82 results on '"Murphy WK"'
Search Results
2. Cisplatin, etoposide, and paclitaxel in the treatment of patients with extensive small-cell lung carcinoma.
- Author
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Glisson BS, Kurie JM, Perez-Soler R, Fox NJ, Murphy WK, Fossella FV, Lee JS, Ross MB, Nyberg DA, Pisters KM, Shin DM, and Hong WK
- Subjects
- Adult, Aged, Carcinoma, Small Cell mortality, Carcinoma, Small Cell pathology, Cisplatin administration & dosage, Disease-Free Survival, Drug Administration Schedule, Etoposide administration & dosage, Female, Humans, Lung Neoplasms mortality, Lung Neoplasms pathology, Male, Middle Aged, Neoplasm Metastasis, Neutropenia chemically induced, Paclitaxel administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Small Cell drug therapy, Lung Neoplasms drug therapy
- Abstract
Purpose: The combination of cisplatin, etoposide, and paclitaxel was studied in patients with extensive small-cell lung cancer in a phase I component followed by a phase II trial to determine the maximum-tolerated dose (MTD), characterize toxicity, and estimate response and median survival rates., Patients and Methods: Forty-one patients were treated between October 1993 and April 1997. Doses for the initial cohort were cisplatin 75 mg/m(2) on day 1, etoposide 80 mg/m(2)/d on days 1 to 3, and paclitaxel 130 mg/m(2) on day 1 over 3 hours. Cycles were repeated every 3 weeks for up to six cycles. The MTD was reached in the first six patients. In these six patients and in the next 35 patients, who were entered onto the phase II trial, response and survival were estimated., Results: At the initial dose level, one of six patients developed febrile neutropenia, and five of six achieved targeted neutropenia (nadir absolute granulocyte count, 100 to 1,000/microL) without any other dose-limiting toxicity, defining this level as the MTD. Grade 4 neutropenia was observed in 88 (47%) of 188 total courses administered at or less than the MTD. Neutropenia was associated with fever in only 17 (9%) of 188 courses, but two patients experienced neutropenic sepsis that was fatal. Nonhematologic toxicity greater than grade 2 was observed in 10 (5%) of 188 total courses, with fatigue, peripheral neuropathy, and nausea/vomiting most common. The overall objective response rate was 90% of 38 assessable patients: six complete responses (16%) and 28 partial responses(74%). Median progression-free and overall survival durations were 31 and 47 weeks, respectively., Conclusion: The combination of cisplatin, etoposide, and paclitaxel produced response and survival rates similar to those of other combinations and was well tolerated.
- Published
- 1999
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3. A pilot clinical laboratory trial of paclitaxel and endobronchial brachytherapy in patients with non-small cell lung cancer.
- Author
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Lee JS, Komaki R, Morice RC, Ro JY, Kalapurakal SK, Schea R, Murphy WK, Shin DM, Fox NT, Walsh GL, Hittelman WN, and Hong WK
- Subjects
- Aged, Antineoplastic Agents, Phytogenic adverse effects, Carcinoma, Non-Small-Cell Lung pathology, Combined Modality Therapy, Female, Granulocyte Colony-Stimulating Factor administration & dosage, Humans, Immunohistochemistry, Infusions, Intravenous, Lung Neoplasms pathology, Male, Middle Aged, Paclitaxel adverse effects, Pilot Projects, Radiation-Sensitizing Agents adverse effects, Survival Analysis, Treatment Outcome, Antineoplastic Agents, Phytogenic administration & dosage, Brachytherapy methods, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung radiotherapy, Lung Neoplasms drug therapy, Lung Neoplasms radiotherapy, Paclitaxel administration & dosage, Radiation-Sensitizing Agents administration & dosage
- Abstract
Paclitaxel enhances microtubule assembly and causes a cell cycle arrest in mitosis, the most radiosensitive phase. We conducted this study to improve our understanding of paclitaxel effects in vivo and to determine the maximum tolerated dose of paclitaxel preceding endobronchial radiation therapy (brachytherapy). The treatment consisted of two cycles of paclitaxel infused over 24 hours followed by 192Ir brachytherapy; cycles were repeated every 3 weeks. Tumor samples were obtained at baseline, after each paclitaxel infusion, and 3 weeks after completion of therapy. Twenty-two non-small cell lung cancer patients with a documented endobronchial lesion were enrolled in the study and 20 patients received the therapy with different doses of paclitaxel, initially without and then later with granulocyte colony-stimulating factor (G-CSF) support (5 microg/kg subcutaneously on days 3 to 10). With the starting paclitaxel dose of 135 mg/m2, five of seven patients developed neutropenia and fever, which mandated a dose reduction to 120 mg/m2. At this dose level, three of three patients had neutropenic fever; thus, 120 mg/m2 of paclitaxel was considered above the maximum tolerated dose without G-CSF support. However, with G-CSF support the therapy was well-tolerated without dose-limiting toxicity and accrual is continuing at the paclitaxel 175-mg/m2 dose level. While no patient had achieved systemic tumor response, 11 patients achieved partial response of the endobronchial lesion, which represents 68.8% of 16 patients who received two courses of therapy and 91.8% of 12 patients who had full evaluation by bronchoscopy after completion of therapy. The in vivo paclitaxel effects were studied using the pre- and post-paclitaxel therapy tumor samples in eight patients. Four (50%) patients had a significant increase in mitotic cells after paclitaxel, as assessed by MPM-2 immunostaining that recognizes a large family of mitotic phosphoproteins. A substantial increase in the number of micronucleated apoptotic cells, another paclitaxel effect, was also found in six patients. These results clearly indicate that patients with endobronchial lesions from recurrent NSCLC could not tolerate this combined modality regimen without G-CSF support. However, this group of patients provided a unique opportunity to study in vivo paclitaxel effects in a clinical trial setting.
- Published
- 1999
4. Phase II trial of recombinant IFN-alpha2a with etoposide/cisplatin induction and interferon/megestrol acetate maintenance in extensive small cell lung cancer.
- Author
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Khuri FR, Fossella FV, Lee JS, Murphy WK, Shin DM, Markowitz AB, and Glisson BS
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Cisplatin administration & dosage, Etoposide administration & dosage, Female, Humans, Interferon alpha-2, Interferon-alpha administration & dosage, Male, Megestrol Acetate therapeutic use, Middle Aged, Recombinant Proteins, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Small Cell drug therapy, Lung Neoplasms drug therapy
- Abstract
Previous data suggested interaction of cisplatin with interferon (IFN) in non-small cell lung cancer and a possible effect of IFN in maintaining remission in small cell lung cancer (SCLC). This study was designed to further examine the effect of IFN in the treatment of extensive disease (ED) SCLC. Forty previously untreated patients with performance status (PS) of 0-2 (Zubrod scale) were treated with etoposide (100 mg/m2 for 3 days), cisplatin (25 mg/m2 for 3 days) (EP), and recombinant IFN-alpha2a (rIFN-alpha2a) (5 x 10(6) U/m2 for 3 days) for six cycles (induction), followed by rIFN-alpha2a (5 x 10(6) U/m2) thrice weekly and megestrol acetate (40 mg q.i.d.) as maintenance therapy for 6 months or until progressive disease or intolerable toxicity was documented. Patients were 25 men (62%) and 15 women (38%), median age 58 (28-76), median Zubrod performance status 1 (0-2). Major sites of metastasis include liver (55%), bone (42%), bone marrow (25%), and adrenal gland (18%). Of 40 eligible patients accrued to this trial, 35 were evaluable for response, and 37 were evaluable for toxicity. There were 3 complete and 28 partial responses, for an overall response rate of 89%. With 39 of 40 patients followed until death, median survival (Kaplan-Meier) is estimated at 46 weeks (95% CI range 35-55). Twenty patients completed six cycles of induction, and 16 received maintenance therapy, median 2 cycles (range 1-3). Major toxicity during induction included grade 4 granulocytopenia in 24%, grade 2-3 nausea or vomiting or both in 41%, grade 2 fatigue in 24%, grade 2 anorexia in 22%, and grade 2-3 renal insufficiency in 9% of 175 total courses of chemotherapy administered. Toxicity during the maintenance phase was notable for grade 2-3 fatigue in 43%, grade 2-3 anorexia in 24%, grade 2-3 weight loss in 10%, and grade 3-4 anemia in 17% of 30 courses. There were no treatment-related deaths. The addition of rIFN-alpha2a to EP in induction chemotherapy of ED SCLC, followed by rIFN-alpha2a and megestrol acetate maintenance therapy, was reasonably well tolerated. The complete and overall response rates and duration of remission and survival appear to be similar to those generally obtained with EP alone in similar patients.
- Published
- 1998
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5. Integration of filgrastim into chemoradiation for limited small cell lung cancer: a Phase I study.
- Author
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Glisson B, Komaki R, Lee JS, Shin DM, Fossella F, Murphy WK, Kurie J, Perez-Soler R, Schea R, and Vadhan-Raj S
- Subjects
- Adult, Aged, Carcinoma, Small Cell pathology, Cisplatin administration & dosage, Cohort Studies, Combined Modality Therapy, Disease-Free Survival, Etoposide administration & dosage, Female, Fever etiology, Filgrastim, Humans, Ifosfamide administration & dosage, Lung Neoplasms pathology, Male, Middle Aged, Neutropenia etiology, Recombinant Proteins, Thrombocytopenia etiology, Thrombocytopenia prevention & control, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Small Cell drug therapy, Carcinoma, Small Cell radiotherapy, Granulocyte Colony-Stimulating Factor administration & dosage, Lung Neoplasms drug therapy, Lung Neoplasms radiotherapy, Neutropenia prevention & control
- Abstract
Purpose: Recent studies document the value of early combined modality therapy of small cell lung cancer, but also indicate that early thoracic radiation adds to myelosuppression and can complicate further chemotherapy. Other studies indicate that simultaneous use of growth factors with thoracic radiation may be deleterious. However, temporal separation of growth factor use from cytotoxic therapy may allow dose intensity to be maintained/enhanced during combined modality treatment. We sought to integrate filgrastim into a novel chemoradiation regimen for patients with limited small cell lung cancer using an approach that separated growth factor administration from both chemotherapy and thoracic radiation., Methods and Materials: Twenty-seven patients with limited disease small cell lung cancer were enrolled in a Phase I trial of cisplatin, ifosfamide/mesna, oral etoposide, and thoracic radiation (1.5 Gy b.i.d. x 30 fractions days 1-19 cycle 1) +/- filgrastim (5 microg/kg/day). Filgrastim was given on days 20-25 of cycle 1 after completion of radiation and following completion of oral etoposide in subsequent cycles. The primary end point was determination of maximum tolerated dose (MTD) of chemotherapy. Serial cohorts were treated with and without filgrastim., Results: Because of dose-limiting thrombocytopenia, primarily, and nonhematologic toxicity, the MTDs with and without filgrastim were identical (cisplatin 20 mg/m2 i.v. and ifosfamide 1200 mg/m2 i.v., both given days 1-3, and etoposide 40 mg/m2 p.o. days 1-14). Filgrastim use shortened the duration of neutropenia at the MTD (median 4 vs. 7 days), but was not associated with a reduction in febrile neutropenia. Although growth factor administration did not allow dose escalation of this regimen, it did allow chemotherapy doses to be maintained at the MTD more frequently through four cycles of therapy. In the 24 evaluable patients, the overall response rate was 100% (71% partial and 29% complete)., Conclusions: Despite careful attention to the timing of growth factor with chemoradiation, the administration of filgrastim with this regimen did not allow dose escalation. As in many other recent studies of hematopoietic growth factors given prophylactically with chemotherapy, the duration of neutropenia at the MTD was shortened and the need for dose reduction throughout treatment was reduced in patients receiving filgrastim at the MTD.
- Published
- 1998
- Full Text
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6. Cisplatin, ifosfamide, and prolonged oral etoposide in the treatment of patients with extensive small cell lung carcinoma.
- Author
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Glisson B, Lee JS, Palmer J, Fossella F, Shin DM, Murphy WK, Perez-Soler R, and Hong WK
- Subjects
- Administration, Oral, Adult, Aged, Antineoplastic Agents adverse effects, Antineoplastic Agents, Alkylating adverse effects, Antineoplastic Agents, Phytogenic adverse effects, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Cisplatin adverse effects, Disease-Free Survival, Etoposide adverse effects, Female, Granulocytes drug effects, Humans, Ifosfamide adverse effects, Leukocyte Count, Male, Middle Aged, Nausea chemically induced, Neoplasm Staging, Neutropenia chemically induced, Remission Induction, Survival Rate, Thrombocytopenia chemically induced, Vomiting chemically induced, Antineoplastic Agents administration & dosage, Antineoplastic Agents, Alkylating administration & dosage, Antineoplastic Agents, Phytogenic administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Small Cell drug therapy, Cisplatin administration & dosage, Etoposide administration & dosage, Ifosfamide administration & dosage, Lung Neoplasms drug therapy
- Abstract
Background: The combination of cisplatin, ifosfamide, and prolonged oral etoposide (PIE) was studied in patients with extensive small cell lung carcinoma (SCLC) in a Phase I trial followed by a Phase II trial to determine the maximum tolerated dose (MTD), characterize toxicity, and estimate response and median survival rates., Methods: Thirty-three patients were treated between October 1991 and December 1994. Doses for the initial cohort were cisplatin 20 mg/m2/day, ifosfamide 1500 mg/m2/day with mesna (all given intravenously on Days 1-3), and oral etoposide 50 mg/m2 on Days 4-17. This cycle was repeated every 4 weeks for up to 6 cycles. The MTD was reached for the first 9 patients. For these 9 patients and the next 24 patients, who were entered in the Phase II trial, response and survival were estimated., Results: Dose-limiting toxicity was manifested as Grade 4 neutropenia in 3 of 3 patients (associated with fever in 2 of 3), and Grade 4 thrombocytopenia was encountered in 2 of 3 patients at the second dose level. Of 6 patients treated at the first dose level, 4 achieved targeted myelosuppression (absolute granulocyte count nadir <1000), but only 1 experienced Grade 4 neutropenia, defining this level as the MTD. Grade 4 neutropenia and/or thrombocytopenia was observed in 36 (24%) of a total of 152 courses administered at or below the MTD. Nonhematologic toxicity above Grade 2 was uncommon, excluding nausea and vomiting. Overall objective response rate was 93% of 30 evaluable patients: 5 (17%) complete responses and 23 partial responses (76%). Median failure free and overall survival durations were 36 and 54 weeks, respectively., Conclusions: The combination of cisplatin, ifosfamide, and oral etoposide produced encouraging failure free and overall median survival rates in patients with extensive SCLC. These results warrant further evaluation of this regimen in the initial therapy of patients with limited stage disease.
- Published
- 1998
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7. Phase I clinical and pharmacological study of liposome-entrapped NDDP administered intrapleurally in patients with malignant pleural effusions.
- Author
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Perez-Soler R, Shin DM, Siddik ZH, Murphy WK, Huber M, Lee SJ, Khokhar AR, and Hong WK
- Subjects
- Adenocarcinoma drug therapy, Adult, Aged, Aged, 80 and over, Animals, Antineoplastic Agents pharmacokinetics, Drug Carriers, Female, Humans, Liposomes, Lung Neoplasms drug therapy, Male, Mesothelioma drug therapy, Metabolic Clearance Rate, Middle Aged, Organoplatinum Compounds pharmacokinetics, Ovarian Neoplasms drug therapy, Pleura, Pleural Neoplasms drug therapy, Rats, Antineoplastic Agents administration & dosage, Antineoplastic Agents adverse effects, Organoplatinum Compounds administration & dosage, Organoplatinum Compounds adverse effects, Pleural Effusion, Malignant drug therapy
- Abstract
cis-Bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum(II) (NDDP) is a lipophilic non-cross-resistant platinum compound formulated in large multilamellar liposomes (1-3 micrometer). The maximum tolerated dose (MTD) of liposomal-entrapped NDDP (L-NDDP) administered i.v. in humans is 300 mg/m2, and myelosuppresion is the dose-limiting toxicity. L-NDDP administered i.p. is absorbed slowly from the peritoneal cavity of rats. Recently, i.p. cisplatin has been shown to be superior to i.v. cisplatin in improving the survival of patients with ovarian carcinoma and minimal residual disease. We conducted a Phase I study to determine the MTD, side effects, kinetics of absorption into the systemic circulation, and preliminary antitumor activity of L-NDDP administered intrapleurally in patients with free-flowing malignant pleural effusions. Twenty-one patients were treated with escalating doses of L-NDDP by intrapleural administration over 30 min every 21 days. Fourteen patients had adenocarcinoma of the lung, 5 patients had malignant pleural mesothelioma (MPM), and 2 patients had ovarian carcinoma. The dose-limiting toxicity of L-NDDP was chest pain secondary to chemical pleuritis, which was severe in three of four patients treated at 550 mg/m2. The MTD was 450 mg/m2. At this dose, the only toxicity observed was grade 1-2 nausea and vomiting presenting 6-8 h after drug administration. Neither myelosuppression nor nephrotoxicity was observed. Loculation of residual pleural fluid with continued decrease over a period of weeks to months was observed in seven patients; in one of these patients (MPM), the pleural effusion disappeared without evidence of recurrence for 19 + months, and in six patients (three adenocarcinoma of the lung, two MPM, and one ovarian carcinoma), the pleural effusion was reduced by >50% for 5+, 10+, 18+, 8, 5+, and 2+ months. Plasma pharmacokinetic studies showed that the absorption of L-NDDP from the pleural cavity was rapid during the first 2 h, with levels becoming steady (bioavailable or free platinum) or increasing slowly (total plasma platinum) between 6 and 24 h after administration. Urinary excretion was negligible (1-3%). We conclude that: (a) the MTD of intrapleural L-NDDP is 50% higher than the MTD after i.v. administration; (b) intrapleural L-NDDP causes mild nausea and vomiting and no myelosuppression at the MTD; and (c) the absorption of L-NDDP into the systemic circulation is much slower than that of the parent compound cisplatin. Because of the favorable depot effect, lack of systemic toxicity, and control of the pleural effusion in three of five patients with MPM, a disease similar to ovarian carcinoma in that it tends to remain confined to a body cavity, a Phase II study of intrapleural L-NDDP administered in patients with MPM is in progress.
- Published
- 1997
8. Maximum-tolerated dose defined for single-agent gemcitabine: a phase I dose-escalation study in chemotherapy-naive patients with advanced non-small-cell lung cancer.
- Author
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Fossella FV, Lippman SM, Shin DM, Tarassoff P, Calayag-Jung M, Perez-Soler R, Lee JS, Murphy WK, Glisson B, Rivera E, and Hong WK
- Subjects
- Adult, Aged, Antimetabolites, Antineoplastic adverse effects, Carcinoma, Non-Small-Cell Lung pathology, Deoxycytidine administration & dosage, Deoxycytidine adverse effects, Drug Administration Schedule, Female, Humans, Lung Neoplasms pathology, Male, Middle Aged, Neoplasm Staging, Gemcitabine, Antimetabolites, Antineoplastic administration & dosage, Carcinoma, Non-Small-Cell Lung drug therapy, Deoxycytidine analogs & derivatives, Lung Neoplasms drug therapy
- Abstract
Purpose: We conducted a phase I trial of the novel nucleoside analog, gemcitabine, in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC) to determine the maximum-tolerated dose and efficacy in this population., Patient and Methods: Eligibility requirements included stage III or IV NSCLC, performance status < or = 1, and no prior chemotherapy. Gemcitabine was administered as a 30-minute intravenous infusion weekly for 3 weeks every 4 weeks. We enrolled patients at doses that ranged from 1,000 to 2,800 mg/m2/wk (three patients per cohort). Responses were assessed after every two courses (8 weeks)., Results: We treated 33 chemotherapy-naive patients with stage III (n = 5) or IV (n = 28) NSCLC. Most had performance status 1, and 67% had adenocarcinoma. Eight of 32 assessable patients (25%) achieved a partial response. The projected median survival duration (all patients) is 49 weeks. The maximum-tolerated dose was 2,200 mg/m2/wk for 3 weeks every 4 weeks; dose-limiting toxicity was myelosuppression and reversible transaminase elevation. Other side effects were consistently mild. The maximum dose-intensity achieved with the first two cycles was 2,362 mg/m2/wk for 3 weeks every 4 weeks, which is a feasible phase II starting dose., Conclusion: This study estimates a phase II starting dose of gemcitabine in chemotherapy-naive patients to be 2,400 mg/m2/wk for 3 consecutive weeks every 4 weeks; this is much higher than that previously reported in heavily pretreated patients. Twenty-five percent of patients with advanced NSCLC achieved a partial response to gemcitabine. This significant activity in conjunction with a very favorable toxicity profile supports the further evaluation of gemcitabine in combination with other active agents.
- Published
- 1997
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9. Treatment of patients with small-cell lung cancer refractory to etoposide and cisplatin with the topoisomerase I poison topotecan.
- Author
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Perez-Soler R, Glisson BS, Lee JS, Fossella FV, Murphy WK, Shin DM, and Hong WK
- Subjects
- Adult, Aged, Aged, 80 and over, Agranulocytosis chemically induced, Antineoplastic Agents adverse effects, Camptothecin adverse effects, Camptothecin therapeutic use, Cisplatin adverse effects, Cisplatin therapeutic use, Drug Resistance, Neoplasm, Etoposide adverse effects, Etoposide therapeutic use, Female, Humans, Male, Middle Aged, Thrombocytopenia chemically induced, Topotecan, Antineoplastic Agents therapeutic use, Camptothecin analogs & derivatives, Carcinoma, Small Cell drug therapy, Lung Neoplasms drug therapy
- Abstract
Purpose: This study was designed to assess the anti-tumor activity of topotecan (TPT) in patients with small-cell lung cancer (SCLC) refractory to etoposide., Patients and Methods: Refractoriness to etoposide was defined as lack of response to etoposide-containing frontline therapy, or progression during or within 3 months of the last dose of etoposide-containing frontline or second-line therapy. Other eligibility criteria were presence of measurable disease, Zubrod scale performance status (PS) < or = 2, < or = two prior chemotherapy regimens, and adequate renal and liver function. TPT was administered at a dose of 1.25 mg/m2/d for 5 days over 30 minutes every 21 days., Results: Thirty-two patients were registered, of whom 28 are fully assessable. All patients had been treated with frontline etoposide and cisplatin. Three patients (11%) achieved a partial remission (PR) (durations, 7, 8, and 19 weeks) and two (7%) achieved a minor response; five patients (17%) had stable disease and 18 (65%) had progressive disease. One of the three patients who achieved a PR had failed to respond to frontline cisplatin and etoposide. The overall median survival duration was 20 weeks. Grade 3 to 4 granulocytopenia and thrombocytopenia occurred after 70% and 31% of courses administered, respectively. No grade 3 to 4 non-hematological toxicities were observed. Grade 1 or 2 nonhematological toxicities (in percentage of patients) consisted of nausea (41%, 8%) and vomiting (25%, 11%), and alopecia (100%)., Conclusion: TPT at the dose and schedule used has modest antitumor activity in SCLC patients refractory to etoposide and cisplatin, which indicates that clinical resistance to the topoisomerase II poison etoposide does not confer cross-sensitivity to the topoisomerase I poison TPT. TPT is well tolerated, with myelosuppression of short duration being the most common and limiting toxicity.
- Published
- 1996
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10. Phase II study of topotecan in patients with advanced non-small-cell lung cancer previously untreated with chemotherapy.
- Author
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Perez-Soler R, Fossella FV, Glisson BS, Lee JS, Murphy WK, Shin DM, Kemp BL, Lee JJ, Kane J, Robinson RA, Lippman SM, Kurie JM, Huber MH, Raber MN, and Hong WK
- Subjects
- Adenocarcinoma drug therapy, Adult, Aged, Antineoplastic Agents administration & dosage, Antineoplastic Agents adverse effects, Camptothecin administration & dosage, Camptothecin adverse effects, Camptothecin therapeutic use, Carcinoma drug therapy, Carcinoma, Non-Small-Cell Lung mortality, Carcinoma, Squamous Cell drug therapy, Female, Humans, Leukopenia chemically induced, Lung Neoplasms mortality, Male, Middle Aged, Survival Rate, Thrombocytopenia chemically induced, Topotecan, Treatment Outcome, Antineoplastic Agents therapeutic use, Camptothecin analogs & derivatives, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms drug therapy
- Abstract
Purpose: This study was designed to assess the anti-tumor activity of topotecan (TPT) in patients with advanced non-small-cell lung cancer (NSCLC) previously untreated with chemotherapy., Patients and Methods: Patients with stage IIIB or IV NSCLC with measurable disease in nonradiated fields were eligible. Other eligibility criteria were Zubrod performance status (PS) < or = 2 and adequate renal and liver function. TPT was administered at a dose of 1.5 mg/m2/d for 5 days over 30 minutes every 21 days. Of 48 registered patients, 40 were fully assessable. Nineteen patients had adenocarcinoma (AD), 14 squamous carcinoma (SCC), and seven poorly differentiated carcinoma., Results: Six patients (15%) achieved a partial remission (PR) (durations: 8, 14, 18, 28, 56, and 61 weeks) and four patients a minor response; 10 patients had stable disease and 20 patients progressive disease. The PR rate was 36% (five of 14 patients) in patients with SCC versus 4% (one of 26 patients) in those with other histologies (P = .014). The overall median survival time was 38 weeks and 30% of patients were alive at 1 year. Grade 3 to 4 granulocytopenia and thrombocytopenia occurred after 76% and 10% of courses administered, respectively. No grade 3 to 4 nonhematologic toxicities were observed. Grade 1 or 2 nonhematologic toxicities consisted of nausea (46% and 5%), vomiting (31% and 7%), and fatigue (53% and 16%)., Conclusion: TPT at the dose and schedule used has moderate antitumor activity in NSCLC; its activity is mostly limited to patients with SCC. TPT is well tolerated, with myelosuppression of short duration being the most common and limiting toxicity.
- Published
- 1996
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11. Prospective study of combination chemotherapy with cyclophosphamide, doxorubicin, and cisplatin for unresectable or metastatic malignant pleural mesothelioma.
- Author
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Shin DM, Fossella FV, Umsawasdi T, Murphy WK, Chasen MH, Walsh G, Komaki R, McMurtrey MJ, and Hong WK
- Subjects
- Adult, Aged, Agranulocytosis chemically induced, Antibiotics, Antineoplastic adverse effects, Antineoplastic Agents adverse effects, Antineoplastic Agents, Alkylating adverse effects, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Cisplatin adverse effects, Cyclophosphamide adverse effects, Disease Progression, Disease-Free Survival, Doxorubicin adverse effects, Drug Administration Schedule, Female, Fever chemically induced, Humans, Male, Mesothelioma secondary, Middle Aged, Nausea chemically induced, Neutropenia chemically induced, Prospective Studies, Remission Induction, Survival Rate, Vomiting chemically induced, Antibiotics, Antineoplastic administration & dosage, Antineoplastic Agents administration & dosage, Antineoplastic Agents, Alkylating administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cisplatin administration & dosage, Cyclophosphamide administration & dosage, Doxorubicin administration & dosage, Mesothelioma drug therapy, Pleural Neoplasms drug therapy
- Abstract
Background: This study was designed to determine the efficacy and side effects of a combination of cyclophosphamide (C), doxorubicin (D), and cisplatin (P) in patients with inoperable, unresectable, or metastatic malignant pleural mesothelioma., Methods: Twenty-three patients with unresectable or metastatic malignant pleural mesothelioma were entered onto the study. The median age was 62 years (range, 42-74 years); there were 20 males and 3 females; the median performance status was 1 (Zubrod's scale). The histologic types included epithelial (14 patients), sarcomatoid (4 patients), unclassified (4 patients), and mixed type (1 patient). Twenty patients were known to have been exposed to asbestos and 3 were not. All patients were treated with the following starting dose of chemotherapy: a cycle comprised of C, 500 mg/m2 intravenously, day 1; D, 50 mg/m2 intravenously, day 1; and P, 80 mg/m2 intravenously, day 1 every 3 weeks. The cisplatin dose was reduced to 50 mg/m2 for the subsequent courses. For the assessment of tumor response, all patients had computed tomography scans of the chest after each three cycles of chemotherapy., Results: Overall, 7 of 23 patients (30%) had partial responses (durations of responses [weeks]: 158+, 91+, 70+, 41+, 40, 39, 25), three had minor responses, and 14 had stable or progressive disease. One partial responder later underwent surgical resection and no viable tumors cells were found in the pathologic specimen. All patients have stopped treatment, and eight are still alive. The most common side effect was granulocytopenia (grade 4, 52%; grade 3, 17%). Other hematologic side effects were modest. Nonhematologic side effects included mild to moderate nausea and vomiting, neutropenic fever (three patients), peripheral neuropathy (one patient), and congestive heart failure (one patient). The overall median duration of survival was 60 weeks., Conclusion: Combination chemotherapy with CDP was well tolerated and had significant activity against unresectable or metastatic malignant pleural mesothelioma. The median duration of responses was 60 weeks; however, the survival rate was far from satisfactory. Continued development of new approaches including the biologic understanding of tumor development and testing new agents is warranted.
- Published
- 1995
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12. Phase II study of docetaxel for advanced or metastatic platinum-refractory non-small-cell lung cancer.
- Author
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Fossella FV, Lee JS, Shin DM, Calayag M, Huber M, Perez-Soler R, Murphy WK, Lippman S, Benner S, and Glisson B
- Subjects
- Adenocarcinoma drug therapy, Adenocarcinoma mortality, Adenocarcinoma pathology, Adult, Aged, Antineoplastic Agents, Phytogenic adverse effects, Carboplatin therapeutic use, Carcinoma, Non-Small-Cell Lung mortality, Carcinoma, Non-Small-Cell Lung pathology, Cisplatin therapeutic use, Docetaxel, Drug Hypersensitivity etiology, Drug Resistance, Female, Follow-Up Studies, Humans, Lung Neoplasms mortality, Lung Neoplasms pathology, Male, Middle Aged, Neoplasm Metastasis, Neutropenia chemically induced, Paclitaxel adverse effects, Paclitaxel therapeutic use, Remission Induction, Survival Rate, Antineoplastic Agents, Phytogenic therapeutic use, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms drug therapy, Paclitaxel analogs & derivatives, Taxoids
- Abstract
Purpose: We conducted a phase II study to determine the response to and toxicity of docetaxel (Taxotere; Rhône-Poulenc Rorer Pharmaceuticals, Inc, Collegeville, PA) in patients with advanced non-small-cell lung cancer refractory to prior platinum-containing chemotherapy (PCC) regimens., Patients and Methods: Forty-four patients with stage IIIb or IV platinum-refractory non-small-cell lung cancer were treated with 100 mg/m2 of docetaxel intravenously over 1 hour every 3 weeks. The responses of 42 of 44 patients were assessable. Most patients had a Zubrod performance status of 1; the predominant histologic type was adenocarcinoma (61%), and 91% of patients had stage IV disease., Results: Nine of 42 assessable patients (21%) achieved a partial response to treatment. The median response duration (from response to progression) was 17 weeks, and the projected median survival duration of all patients is 42 weeks (51 weeks for adenocarcinoma and 22 weeks for nonadenocarcinoma). Grade 3/4 neutropenia occurred in 85% of patients and was associated with fever that required intravenous antibiotics in 16% of patients (3% of cycles). Other acute side effects included easily treated hypersensitivity reactions and dermatitis. Cumulative side effects included fluid retention and neuropathy., Conclusion: Docetaxel administered at 100 mg/m2 intravenously every 3 weeks has notable activity against platinum-refractory non-small-cell lung cancer, with a 21% major response rate. Primary side effects were neutropenia, hypersensitivity, and fluid retention.
- Published
- 1995
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13. Interdigitating versus concurrent chemotherapy and radiotherapy for limited small cell lung cancer.
- Author
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Komaki R, Shin DM, Glisson BS, Fossella FV, Murphy WK, Garden AS, Oswald MJ, Hong WK, Roth JA, and Peters LJ
- Subjects
- Adult, Aged, Carcinoma, Small Cell mortality, Carcinoma, Small Cell pathology, Cisplatin administration & dosage, Combined Modality Therapy, Cranial Irradiation, Cyclophosphamide administration & dosage, Doxorubicin administration & dosage, Drug Administration Schedule, Etoposide administration & dosage, Female, Humans, Lung Neoplasms mortality, Lung Neoplasms pathology, Lymphatic Metastasis, Male, Middle Aged, Neoplasm Recurrence, Local, Remission Induction, Treatment Failure, Vincristine administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Small Cell drug therapy, Carcinoma, Small Cell radiotherapy, Lung Neoplasms drug therapy, Lung Neoplasms radiotherapy
- Abstract
Purpose: Sequencing and timing of chemotherapy and radiotherapy for limited small-cell lung cancer (LSCLC) was studied in two consecutive trials., Methods and Materials: In the interdigitating (IDG) trial, three cycles of COPE (cyclophosphamide 750 mg/M2 i.v. Day 1, vincristine 2 mg i.v. Day 8, cisplatin [DDP] 20 mg/M2 Days 1-3, etoposide 100 mg/M2 i.v. Days 1-3), were followed by thoracic radiation therapy (1.5 Gy bid 5-6 h apart, repeated twice at 3-week intervals) to give 45 Gy in 9 weeks; COPE was given during the intervals and for two more cycles. Operable patients had thoracotomy followed by IDG. Prophylactic cranial irradiation (PCI), 2.0 Gy x 15 fractions with a total dose of 30 Gy in 3 weeks, was given to the complete responders (CR) after completion of chemotherapy. In the concurrent (CON) trial, patients received DDP 60 mg/M2 i.v. Day 1, and etoposide 120 mg/M2 i.v. Days 1-3 for four cycles, every 3 weeks, and concurrent thoracic radiation therapy to 45 Gy with either 1.8 Gy daily, for 5 weeks or 1.5 Gy bid for 3 weeks. Prophylactic cranial irradiation (PCI) was given to the complete responders, 2.5 Gy daily for 2 weeks (25 Gy) (approximately 3 months after the initiation of treatment)., Results: The IDG group had 28 evaluable patients with median follow-up of 17.5 months. The CON group had 33 evaluable patients with median follow-up of 21 months. Overall survival rates for IDG patients were 79% at 1 year, 39% at 2 years, 30% at 3 years, and 27% at 4 years compared to 93%, 70%, 51%, and 46%, respectively, for the patients treated with CON (p = 0.01). Loco-regional recurrence (44%) and distant metastasis (48%) was more frequent as the first site of failure in the IDG group compared to the CON group (30% and 30%, respectively). Brain metastases constituted 30% of first metastases with IDG compared to none with CON. Esophagitis was significantly greater with CON. Hematologic and pulmonary toxicity were similar with IDG and CON. One death due to infection was seen in each treatment group., Conclusion: Concurrent chemoradiotherapy appears to be more effective than IDG. Earlier administration of PCI with concurrent chemotherapy and thoracic irradiation may reduce the risk of brain metastasis.
- Published
- 1995
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14. Phase II study of docetaxel for recurrent or metastatic non-small-cell lung cancer.
- Author
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Fossella FV, Lee JS, Murphy WK, Lippman SM, Calayag M, Pang A, Chasen M, Shin DM, Glisson B, and Benner S
- Subjects
- Adult, Aged, Antineoplastic Agents, Phytogenic adverse effects, Carcinoma, Non-Small-Cell Lung mortality, Carcinoma, Non-Small-Cell Lung secondary, Docetaxel, Female, Humans, Lung Neoplasms mortality, Male, Middle Aged, Neoplasm Recurrence, Local, Paclitaxel adverse effects, Paclitaxel therapeutic use, Survival Rate, Antineoplastic Agents, Phytogenic therapeutic use, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms drug therapy, Paclitaxel analogs & derivatives, Taxoids
- Abstract
Purpose: We conducted a phase II study to determine the response and toxicity of docetaxel (Taxotere; Rhône-Poulenc Rorer Pharmaceuticals, Inc, Collegeville, PA) in chemotherapy-naive patients with advanced non-small-cell lung cancer., Patients and Methods: We treated 41 chemotherapy-naive patients who had stage IIIb or IV non-small-cell lung cancer with 100 mg/m2 of docetaxel intravenously over 1 hour every 3 weeks. Responses were assessed after every one to two treatment courses. Responses of 39 of 41 patients were assessable. The patient's median age was 63 years; 90% of patients had a Zubrod performance status of 0 or 1. The predominant histology was adenocarcinoma (54%), and 90% of patients had stage IV disease., Results: Thirteen patients (33%) achieved a partial response to treatment, and the median response duration was 14 weeks. Grade 3 or 4 neutropenia occurred in 97% of patient; this was usually of brief duration and was associated with serious infection in 17% of patients. Other acute toxic effects included easily treated hypersensitivity reactions (36% of patients) and dermatitis (74%). We also observed fluid retention (with peripheral edema or pleural effusion or both) in 54% of patients. This was a cumulative side effect that generally occurred late in treatment., Conclusion: Docetaxel administered at 100 mg/m2 intravenously every 3 weeks has significant activity against non-small-cell lung cancer, with a 33% major response rate. Primary toxicities were neutropenia, hypersensitivity, and fluid retention.
- Published
- 1994
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15. A randomized, double-blind comparison of intravenous ondansetron alone and in combination with intravenous dexamethasone in the prevention of high-dose cisplatin-induced emesis.
- Author
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Hesketh PJ, Harvey WH, Harker WG, Beck TM, Ryan T, Bricker LJ, Kish JA, Murphy WK, Hainsworth JD, and Haley B
- Subjects
- Adult, Aged, Aged, 80 and over, Dexamethasone administration & dosage, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Injections, Intravenous, Male, Middle Aged, Neoplasms drug therapy, Ondansetron administration & dosage, Treatment Outcome, Vomiting chemically induced, Cisplatin adverse effects, Dexamethasone therapeutic use, Ondansetron therapeutic use, Vomiting prevention & control
- Abstract
Purpose: This study compares the efficacy and safety of ondansetron alone with that of ondansetron plus dexamethasone in the prevention of emesis induced by high-dose cisplatin (> or = 100 mg/m2)., Patients and Methods: This multicenter study used a randomized, double-blind, parallel-group design. Chemotherapy-naive patients were randomized to receive intravenous (IV) ondansetron (Zofran, Cerenex Pharmaceuticals, Research Triangle Park, NC) 0.15 mg/kg for three doses every 4 hours beginning 30 minutes before cisplatin administration either alone or in combination with dexamethasone 20 mg administered 45 minutes before cisplatin. Cisplatin (> or = 100 mg/m2) was administered as a single infusion (< or = 3 hours). Patients were monitored for emetic episodes (EEs), adverse events, and laboratory safety parameters for 24 hours after cisplatin administration., Results: A total of 275 patients were enrolled. Of these, 245 were assessable for efficacy. Patients who received ondansetron plus dexamethasone had a higher complete antiemetic response rate (61% v 46%, P = .02) and less nausea (posttreatment visual analog scale mean 18.2 v 32.8, P < .001) than did those who received ondansetron alone. The time to the first EE was longer for patients in the group that received ondansetron plus dexamethasone (P = .005). Headache (12%), diarrhea (2%), and abdominal colic (1%) were the most common antiemetic-related adverse events reported. The incidence of adverse events was similar between the treatment groups., Conclusion: IV ondansetron in combination with dexamethasone is safe and more effective than ondansetron alone in the prevention of emesis induced by high-dose cisplatin.
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- 1994
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16. Phase II study of taxol in patients with untreated advanced non-small-cell lung cancer.
- Author
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Murphy WK, Fossella FV, Winn RJ, Shin DM, Hynes HE, Gross HM, Davilla E, Leimert J, Dhingra H, and Raber MN
- Subjects
- Carcinoma, Non-Small-Cell Lung mortality, Carcinoma, Non-Small-Cell Lung pathology, Cimetidine administration & dosage, Dexamethasone administration & dosage, Diphenhydramine administration & dosage, Drug Administration Schedule, Humans, Lung Neoplasms mortality, Lung Neoplasms pathology, Neoplasm Staging, Paclitaxel adverse effects, Premedication, Remission Induction, Carcinoma, Non-Small-Cell Lung surgery, Lung Neoplasms surgery, Paclitaxel therapeutic use
- Abstract
Background: Taxol, a complex plant product (a diterpene) extracted from the bark of Taxus brevifolia, has demonstrated substantial anticancer activity in ovarian and breast cancers, malignant melanoma, and acute myelogenous leukemia. Due to allergic reactions in phase I and early phase II studies, use of a 24-hour infusion of taxol with prophylactic dexamethasone, diphenhydramine, and cimetidine has been recommended., Purpose: In this phase II study, we attempted to determine the efficacy and toxicity of taxol in patients with advanced (stage IIIB or IV) non-small-cell lung cancer who had never received chemotherapy., Methods: Patients were not excluded because of prior surgery or because of radiotherapy administered more than 4 weeks before study entry. Taxol was administered in the hospital at a dose of 200 mg/m2 as an intravenous infusion over 24 hours and repeated every 3 weeks, provided that patients had recovered from any toxic effects. Dexamethasone, cimetidine, and diphenhydramine were given before chemotherapy to prevent hypersensitivity reactions. Therapy was continued for at least two courses unless there was rapid disease progression and for at least three courses if no change was observed and no grade 3 or 4 toxic effects occurred. Treatment was continued for six more courses after maximum response or for two more courses after complete remission but was discontinued if disease progressed., Results: Of the 27 patients entered in the study, 25 were assessable for toxic effects and response. One patient had an allergic reaction that was not life threatening. The overall response rate was 24% (one complete response and five partial responses). An additional seven patients (28%) had minor response. Granulocytopenia was the dose-limiting toxic effect, and neutropenic fever occurred in eight of 118 courses. One additional patient developed neutropenic sepsis with hypotension but recovered with intensive treatment., Conclusions: Taxol appears to have activity against non-small-cell carcinoma of the lung., Implications: A phase II study combining taxol, etoposide, and cisplatin and using hematopoietic stimulating factors is now proposed. The optimal dose for combination chemotherapy has yet to be determined. An important consideration is potential cardiac effects of taxol with other drugs.
- Published
- 1993
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17. Stratified, randomized, double-blind comparison of intravenous ondansetron administered as a multiple-dose regimen versus two single-dose regimens in the prevention of cisplatin-induced nausea and vomiting.
- Author
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Beck TM, Hesketh PJ, Madajewicz S, Navari RM, Pendergrass K, Lester EP, Kish JA, Murphy WK, Hainsworth JD, and Gandara DR
- Subjects
- Adult, Aged, Aged, 80 and over, Double-Blind Method, Drug Administration Schedule, Female, Humans, Injections, Intravenous, Male, Middle Aged, Nausea chemically induced, Vomiting chemically induced, Cisplatin adverse effects, Nausea prevention & control, Ondansetron administration & dosage, Vomiting prevention & control
- Abstract
Purpose: This study compares the efficacy and safety of two single-dose regimens with the approved three-dose regimen of ondansetron in the prevention of cisplatin-induced emesis., Patients and Methods: This multicenter study was a stratified, randomized, double-blind, and parallel group design. Chemotherapy-naive inpatients were randomized to receive intravenous (IV) ondansetron (Zofran; Glaxo Inc, Research Triangle Park, NC) 0.15 mg/kg times three doses, every 4 hours or a single 8-mg or 32-mg dose followed by two saline doses that began 30 minutes before cisplatin administration. Cisplatin (high-dose > or = 100 mg/m2 or medium-dose 50 to 70 mg/m2) was given as a single infusion (< or = 3 hours). Patients were monitored for emetic episodes, adverse events, and laboratory safety parameters for 24 hours after cisplatin administration., Results: A total of 699 patients (359 high-dose, 340 medium-dose) were enrolled. Of these, 618 were assessable for efficacy (15 ineligible, 66 protocol deviations). The 32-mg dose was superior to the 8-mg single dose with regard to total number of emetic episodes (high-dose, P = .015; medium-dose, P < .001), complete response (no emetic episodes: high-dose, 48% v 35%; P = .048; medium-dose, 73% v 50%; P = .001) and failure rate (> 5 emetic episodes, withdrawn or rescued: high-dose, 20% v 34%; P = .018; medium-dose, 9% v 23%; P = .005). The 32-mg single dose was also superior to the 0.15 mg/kg times three dose regimen with regard to total number of emetic episodes (medium-dose, P = .033) and failure rate (high-dose, 20% v 36%; P = .009; medium-dose, 9% v 22%; P = .011). Ondansetron was well tolerated. The most common adverse event was headache. An approximate 10-fold increase in the incidence of clinically significant transaminase elevations was observed in the high-dose versus medium-dose cisplatin strata (aspartate aminotransferase [AST], 6.5% v 0.7%; serum alanine aminotransferase [ALT], 5.0% v 0.3%)., Conclusion: A 32-mg single dose of ondansetron is more effective than a single 8-mg dose and is at least as effective as the standard regimen of 0.15 mg/kg times three doses in the prevention of cisplatin-induced acute emesis.
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- 1992
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18. Improved therapeutic index by leucovorin of edatrexate, cyclophosphamide, and cisplatin regimen for non-small-cell lung cancer.
- Author
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Lee JS, Libshitz HI, Fossella FV, Murphy WK, Pang AC, Lippman SM, Shin DM, Dimery IW, Glisson BS, and Hong WK
- Subjects
- Aminopterin administration & dosage, Aminopterin analogs & derivatives, Cisplatin administration & dosage, Cyclophosphamide administration & dosage, Drug Administration Schedule, Drug Evaluation, Humans, Leucovorin administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms drug therapy
- Published
- 1992
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19. Phase II study of combination therapy with high-dose cisplatin, etoposide, and mitomycin in patients with advanced non-small-cell lung cancer.
- Author
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Shin DM, Dhingra HM, Lee JS, Fossella FV, Murphy WK, and Hong WK
- Subjects
- Adult, Aged, Cisplatin administration & dosage, Drug Evaluation, Etoposide administration & dosage, Female, Humans, Male, Middle Aged, Mitomycins administration & dosage, Survival Analysis, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms drug therapy
- Abstract
Forty-six patients with metastatic non-small-cell lung cancer (NSCLC) were treated with a combination of high-dose cisplatin, etoposide, and mitomycin. Thirty-four patients (74%) had a performance status of 1, and 39 patients (85%) had adenocarcinoma. Of the 42 patients evaluable for response and toxicity, four achieved a partial response (10%); no patient achieved a complete response. Seven patients who had received prior chemotherapy showed no major response. The median survival of all 42 patients was 23 weeks. Myelosuppression was the major dose-limiting toxicity for this regimen, and 12 of 46 patients (26%) developed neutropenic fever requiring hospitalization and parenteral antibiotics. Of the 12 patients with severe neutropenic fever, one patient died because of toxicity. Nonhematologic toxicities, including azotemia, peripheral neuropathy, nausea, vomiting, and hearing loss were transient and modest. We conclude that high-dose cisplatin combined with etoposide and mitomycin is a relatively toxic regimen with a low response rate. Further evaluation of the combination as given in this trial is not warranted.
- Published
- 1992
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20. Edatrexate improves the antitumor effects of cyclophosphamide and cisplatin against non-small cell lung cancer.
- Author
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Lee JS, Libshitz HI, Fossella FV, Murphy WK, Pang AC, Lippman SM, Shin DM, Dimery IW, Glisson BS, and Hong WK
- Subjects
- Adult, Aged, Aminopterin administration & dosage, Aminopterin pharmacology, Antineoplastic Agents administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Cyclophosphamide administration & dosage, Dose-Response Relationship, Drug, Drug Evaluation, Drug Synergism, Female, Humans, Male, Middle Aged, Aminopterin analogs & derivatives, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms drug therapy
- Abstract
The authors treated 32 patients with Stage IIIB or IV non-small cell lung cancer (NSCLC) with an outpatient regimen of edatrexate (10-ethyl-10-deaza-aminopterin) (10-EdAM) on days 1 and 8, cyclophosphamide on day 1, and cisplatin on day 1, repeated every 3 weeks with dose modification. The 22 men and 10 women (median age, 57 years of age) had no prior chemotherapy and a Zubrod performance status less than or equal to 2. A schedule with initial doses of 80 mg/m2, 800 mg/m2, and 80 mg/m2, respectively, yielded a 47% major response rate with two complete responses (95% confidence interval [CI], 25% to 70%), but it also yielded significant stomatitis and myelosuppression. A schedule with reduced starting doses (70 mg/m2, 700 mg/m2, and 70 mg/m2) was better tolerated, but dropped the major response rate to 27% with no complete responses (95% CI, 11% to 52%). Median survival time was 39 weeks for all 30 evaluable patients without a significant difference between the treatment groups (which were comparable in patient characteristics). Major response, however, was associated with longer survival time than minor response or no change (P = 0.024) or progressive disease (P = 0.001) (median survival times, 55, 39, and 27 weeks, respectively). When the doses delivered were compared, patients treated with the reduced dose schedule received less mean 10-EdAM per course (P = 0.01), although the doses of cyclophosphamide and cisplatin were comparable to the original dose schedule for the second course and thereafter. These results suggest that this three-drug regimen may have synergistic antitumor effects, with a steep dose-response relationship, particularly with 10-EdAM. With amelioration of the dose-limiting stomatitis of 10-EdAM, it seems possible to maximize the antitumor effects of this regimen.
- Published
- 1991
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21. A randomized double-blind study of gallium nitrate compared with etidronate for acute control of cancer-related hypercalcemia.
- Author
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Warrell RP Jr, Murphy WK, Schulman P, O'Dwyer PJ, and Heller G
- Subjects
- Adult, Aged, Analysis of Variance, Calcium blood, Creatinine blood, Double-Blind Method, Etidronic Acid adverse effects, Female, Gallium adverse effects, Humans, Hypercalcemia blood, Hypercalcemia etiology, Infusions, Intravenous, Male, Middle Aged, Neoplasms complications, Phosphates blood, Regression Analysis, Etidronic Acid therapeutic use, Gallium therapeutic use, Hypercalcemia drug therapy
- Abstract
Hypercalcemia is a major source of morbidity and mortality in patients with cancer. Gallium nitrate and the bisphosphonate, etidronate, are new agents that have recently become available for treatment of this disorder. To directly compare therapeutic effectiveness, we conducted a randomized, double-blind, multicenter study of gallium nitrate compared with etidronate for acute control of cancer-related hypercalcemia. Gallium nitrate was administered by continuous intravenous (IV) infusion at a dose of 200 mg/m2/d. Etidronate was administered as a 4-hour IV infusion at a dose of 7.5 mg/kg. Both drugs were given daily for 5 consecutive days. Eligible patients had persistent moderate-to-severe hypercalcemia (total serum calcium [corrected for serum albumin] greater than or equal to 12.0 mg/dL) after 2 days of hospitalization and IV hydration. Seventy-one patients were randomized and treated. Twenty-eight of 34 patients (82%) who received gallium nitrate achieved normocalcemia compared with 16 of 37 patients (43%) who received etidronate (P less than .001). Patients who received etidronate required significantly greater amounts of IV fluids (P = .04) and more hypocalcemic drug treatment (P less than .05) during the poststudy period than patients who received gallium nitrate. Kaplan-Meier analysis showed a significantly longer median duration of normocalcemia for patients treated with gallium nitrate (8 days v 0 days, P = .0005). A significantly higher proportion of patients treated with gallium nitrate developed asymptomatic hypophosphatemia compared with patients treated with etidronate (97% v 43%, P less than .001). We conclude that gallium nitrate is highly effective and superior to etidronate for acute control of moderate-to-severe cancer-related hypercalcemia.
- Published
- 1991
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22. Healing of periapical radiolucencies after nonsurgical endodontic therapy.
- Author
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Murphy WK, Kaugars GE, Collett WK, and Dodds RN
- Subjects
- Adult, Age Factors, Aged, Follow-Up Studies, Humans, Middle Aged, Periapical Diseases diagnostic imaging, Radiography, Retrospective Studies, Periapical Diseases physiopathology, Root Canal Therapy, Wound Healing
- Abstract
Eighty-nine periapical radiolucencies treated by nonsurgical endodontic therapy were evaluated to better understand the healing rates of these lesions. After at least 3 months after treatment, radiographs revealed that 46.1% of the lesions had resolved, 48.3% had undergone partial resolution, 2.2% were unchanged, and 3.4% were larger. The average radiographic rate of repair was 3.2 mm2/mo. Less than 6 months after treatment, 17.6% of lesions demonstrated complete radiographic resolution, whereas 70.6% showed radiographic resolution at 12 months or longer.
- Published
- 1991
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23. Phase II trial of 5,6-dihydro-5-azacytidine in pleural malignant mesothelioma.
- Author
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Dhingra HM, Murphy WK, Winn RJ, Raber MN, and Hong WK
- Subjects
- Aged, Aged, 80 and over, Antimetabolites, Antineoplastic adverse effects, Azacitidine adverse effects, Azacitidine therapeutic use, Drug Evaluation, Female, Humans, Male, Middle Aged, Antimetabolites, Antineoplastic therapeutic use, Azacitidine analogs & derivatives, Mesothelioma drug therapy, Pleural Neoplasms drug therapy
- Published
- 1991
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24. Phase I/II clinical trial of didemnin B in non-small-cell lung cancer: neuromuscular toxicity is dose-limiting.
- Author
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Shin DM, Holoye PY, Murphy WK, Forman A, Papasozomenos SC, Hong WK, and Raber M
- Subjects
- Adult, Aged, Antineoplastic Agents administration & dosage, Drug Administration Schedule, Drug Evaluation, Female, Humans, Infusions, Intravenous, Male, Middle Aged, Neuromuscular Junction drug effects, Peptides, Cyclic administration & dosage, Antineoplastic Agents adverse effects, Carcinoma, Non-Small-Cell Lung drug therapy, Depsipeptides, Lung Neoplasms drug therapy, Muscles drug effects, Peptides, Cyclic adverse effects
- Abstract
Didemnin B (NSC 325,319), a cyclic depsipeptide isolated from a Caribbean tunicate, exhibits potent preclinical antitumor activity. In previous phase I studies, 3.47 mg/m2 was the maximally tolerated dose, with nausea and vomiting being the dose-limiting toxicity. The drug was given in a single bolus infusion over 30 min every 28 days. In the current study, 30 patients presenting with previously treated non-small-cell lung cancer (NSCLC) received 46 courses of the drug at doses ranging from 3.47 to 9.1 mg/m2. Neuromuscular toxicity was dose-limiting. Nausea and vomiting appeared to be correlated with dose levels and were ameliorated by a combination of antiemetics including dexamethasone. Other side effects included a mild rise in hepatic enzymes and an allergic reaction that was preventable by the addition of corticosteroids to the premedication regimen. In all, 2 minor responses were seen among 24 evaluable patients. Because neuromuscular toxicity is dose-limiting, we recommend that routine measurements of creatine kinase and aldolase, a careful neurologic evaluation, and electromyography and muscle biopsy (if indicated) be incorporated into phase II trials. The recommended dose for phase II studies using a single bolus schedule is 6.3 mg/m2, following the premedication of patients with antiemetics.
- Published
- 1991
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25. Alleviation by leucovorin of the dose-limiting toxicity of edatrexate: potential for improved therapeutic efficacy.
- Author
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Lee JS, Murphy WK, Shirinian MH, Pang A, and Hong WK
- Subjects
- Aminopterin administration & dosage, Aminopterin adverse effects, Antineoplastic Agents administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Non-Small-Cell Lung complications, Carcinoma, Non-Small-Cell Lung drug therapy, Cisplatin administration & dosage, Cyclophosphamide administration & dosage, Dose-Response Relationship, Drug, Drug Evaluation, Drug Tolerance, Female, Folic Acid Antagonists administration & dosage, Humans, Lung Neoplasms complications, Lung Neoplasms drug therapy, Male, Middle Aged, Stomatitis chemically induced, Stomatitis prevention & control, Aminopterin analogs & derivatives, Antineoplastic Agents adverse effects, Folic Acid Antagonists adverse effects, Leucovorin therapeutic use
- Abstract
Edatrexate (10-ethyl-10-deaza-aminopterin; CGP 30 694) is a methotrexate (MTX) analogue that shows promise against non-small-cell lung cancer (NSCLC) and other tumors. Since edatrexate's mechanism of action is the same as that of MTX, we used leucovorin in an attempt to alleviate its dose-limiting toxicity, stomatitis. In four patients with NSCLC who had experienced significant stomatitis after treatment with edatrexate, cyclophosphamide, and cisplatin, we observed a remarkable reduction in stomatitis following the administration of low-dose leucovorin. On the basis of the results obtained in these individuals, we treated 15 additional patients with this three-drug regimen plus leucovorin rescue. These subjects could tolerate the treatment with lesser degrees of stomatitis and received higher edatrexate doses in subsequent courses as compared with the patients who previously received this regimen without leucovorin rescue. This approach is expected to improve the therapeutic indices of edatrexate and edatrexate-containing chemotherapy regimens by modifying the dose-limiting toxicity of this antineoplastic agent.
- Published
- 1991
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26. Phase II study of 10-ethyl-10-deaza-aminopterin (10-EdAM; CGP 30 694) for stage IIIB or IV non-small cell lung cancer.
- Author
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Lee JS, Libshitz HI, Murphy WK, Jeffries D, and Hong WK
- Subjects
- Adult, Aged, Aminopterin therapeutic use, Aminopterin toxicity, Carcinoma, Non-Small-Cell Lung mortality, Female, Folic Acid Antagonists toxicity, Humans, Lung Neoplasms mortality, Male, Middle Aged, Neoplasm Staging, Pleural Effusion chemically induced, Aminopterin analogs & derivatives, Carcinoma, Non-Small-Cell Lung drug therapy, Folic Acid Antagonists therapeutic use, Lung Neoplasms drug therapy
- Abstract
Thirty-one patients with stage IIIB or IV non-small cell lung cancer (NSCLC) were treated with intravenous 10-EdAM on a weekly basis. The starting dose was 80 mg/m2, with subsequent doses adjusted depending on evidence of toxicity. There were 20 men and 11 women with a median age of 58 years (range, 33-75). Response was evaluated in 30 patients, 5 with evaluable but not measurable tumors and 25 with measurable indicator lesions. There were no complete remissions; 3 patients achieved partial remission. Nine patients had a minor response, 6 showed no change, and 12 had progressive disease. Median survival for all 31 patients was 43 weeks (range, 12-65+). During the first 3-week period, the 10-EdAM dose was reduced or withheld in 19 patients (because of stomatitis in 12, SGPT elevation in 3, skin rash in 2, and granulocytopenia in 2), escalated in 11 patients, and unchanged in 1 patient. A mean of 34-88 mg/m2 of 10-EdAM (median, 50) was given per week during the first 5-week period. Myelotoxicity was infrequent and there was no significant nephrotoxicity. Considering the modest side effects of this treatment and the conservative dose-modification schedule which mandated substantial dose reductions, we conclude that 10-EdAM is a promising antitumor agent for NSCLC.
- Published
- 1990
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27. Intercanthal and interpupillary distance in the black population.
- Author
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Murphy WK and Laskin DM
- Subjects
- Cephalometry, Female, Humans, Hypertelorism pathology, Male, Middle Aged, Orbit anatomy & histology, Pupil, Reference Values, United States, Black or African American, Black People, Skull anatomy & histology
- Abstract
Intercanthal distance is an important measurement in the evaluation of congenital deformities and posttraumatic telecanthus. In this study 100 black patients (71 female and 29 male) were measured for intercanthal and interpupillary distance. For the overall group the mean intercanthal distance was 33.9 +/- 3.0 mm; previous studies of white persons and mixed populations indicate an average of 32 +/- 3 mm. The mean interpupillary distance for this study was 63.7 +/- 3.7 mm; previous studies indicate an average of 63 +/- 3 mm. This study suggests that the intercanthal and interpupillary distances in blacks are similar to findings of previous studies on whites and mixed populations.
- Published
- 1990
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28. Ifosfamide with mesna uroprotection in the management of lung cancer.
- Author
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Holoye PY, Glisson BS, Lee JS, Dhingra HM, Murphy WK, Umsawasdi T, Levy JK, Jeffries D, Raber MN, and Hong WK
- Subjects
- Aged, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Small Cell drug therapy, Female, Humans, Ifosfamide adverse effects, Lung Neoplasms mortality, Male, Middle Aged, Survival Rate, Urologic Diseases chemically induced, Vincristine administration & dosage, Carcinoma, Bronchogenic drug therapy, Ifosfamide therapeutic use, Lung Neoplasms drug therapy, Mercaptoethanol analogs & derivatives, Mesna therapeutic use, Urologic Diseases prevention & control
- Abstract
Fourteen patients with extensive disease small cell bronchogenic carcinoma (SCBC) received ifosfamide at 2,000 mg/m2/day for 5 consecutive days with simultaneous mesna and vincristine while 26 patients with extensive disease non-small-cell bronchogenic carcinoma (N-SCBC) received the same regimen without vincristine. Eight partial responses (57%) were observed with a 40-week median survival in the case of SCBC and four partial remissions (15%) with a 31-week median survival in N-SCBC. Granulocytopenia was the dose-limiting toxicity, whereas urotoxicity was well controlled with mesna. Neuropsychiatric toxicity consisted of anxiety, agitation, confusion, and hallucination. Neurobehavioral testing detected worsened performance during ifosfamide treatment. Ifosfamide is one of the few active agents in N-SCBC.
- Published
- 1990
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29. The role of adjuvant surgery in the combined modality therapy of small-cell bronchogenic carcinoma after a chemotherapy-induced partial remission.
- Author
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Holoye PY, McMurtrey MJ, Mountain CF, Murphy WK, Dhingra HM, Umsawasdi T, Glisson BS, Lee JS, Carr DT, and Valdivieso M
- Subjects
- Adult, Aged, Antineoplastic Agents therapeutic use, Carcinoma, Bronchogenic drug therapy, Carcinoma, Bronchogenic mortality, Carcinoma, Bronchogenic pathology, Combined Modality Therapy, Female, Humans, Lung Neoplasms drug therapy, Lung Neoplasms mortality, Lung Neoplasms pathology, Male, Middle Aged, Prognosis, Remission Induction, Carcinoma, Bronchogenic surgery, Lung Neoplasms surgery
- Abstract
Twenty-six patients with a limited-disease presentation of small-cell bronchogenic carcinoma (SCBC) had surgery after achieving a partial remission with three cycles of chemotherapy. Persistent SCBC was found in 15 patients (58%), non-small-cell bronchogenic carcinoma (NSCBC) in six patients (23%), and no malignancy in five patients (19%). Twelve patients have died since surgery. Tumor-node-metastasis (TNM) staging prior to or after chemotherapy was not predictive of outcome, but an N0 status found at pathological examination of the surgical specimen was predictive of long-term survival. Median survival for this group of patients was 25 months. Adjuvant surgery is feasible and may be beneficial.
- Published
- 1990
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30. Long-Term Results of CAP Therapy in Chronic Lymphocytic Leukemia.
- Author
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Keating MJ, Hester JP, McCredie KB, Burgess MA, Murphy WK, and Freireich EJ
- Abstract
This study was designed to study the efficacy and toxicity of an adriamycin-containing regimen (CAP: cyclophosphamide, adriamycin, and prednisone) in patients with previously untreated chronic lymphocytic leukemia (CLL). CAP was given to clinical complete remission followed by 18 months of cyclophosphamide-prednisone (CP) maintenance. Forty-seven patients with previously untreated CLL were treated. These patients initially presented with advanced stage (Rai III or IV) or had less advanced stage (Rai 0-II) patients and demonstrated evidence of disease progression. Patients received 750 mg/m(2) of cyclophosphamide intravenously on day 1, 50 mg/m(2) of adriamycin intravenously on day 1 and 100 mg/day of prednisone on days 1-5. Courses were repeated at 3-week intervals until clinical CR, at which time maintenance with cyclophosphamide and prednisone (CP) was commenced. A maximum cumulative dose of 450 mg/m(2) of adriamycin (9 courses of CAP) was given. Twenty (43%) of 47 patients obtained a CR and 11 (23%) obtained a partial remission. Bone marrow biopsy criteria were used to define response in addition to clinical and peripheral blood responses. All patients have been followed for 10 years. The median survival was 259 weeks. No patient remains in remission. No impact of response on survival was found. Surprisingly, the response rate and survival were higher and longer for patients with more advanced stages and higher tumor burdens. The median survival times for patients with Rai stage IV and Binet stage C disease were 93 months and 81 months, respectively. Although the regimen was well tolerated, three patients, each with an antecedent cardiac risk factor, developed congestive heart failure. Adriamycin containing regimens can be safely given to elderly patients with CLL and show promise in the treatment of advanced stage disease.
- Published
- 1990
- Full Text
- View/download PDF
31. Beta-lactam regimens for the febrile neutropenic patient.
- Author
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Bodey GP, Fainstein V, Elting LS, Anaissie E, Rolston K, Khardori N, Kantarjian H, Plager C, Murphy WK, and Holmes F
- Subjects
- Adolescent, Adult, Aged, Anti-Bacterial Agents adverse effects, Anti-Bacterial Agents therapeutic use, Ceftazidime administration & dosage, Clavulanic Acid, Clavulanic Acids administration & dosage, Female, Fever drug therapy, Humans, Male, Middle Aged, Ticarcillin administration & dosage, Vancomycin administration & dosage, Agranulocytosis complications, Anti-Bacterial Agents administration & dosage, Bacterial Infections drug therapy, Neutropenia complications
- Abstract
A total of 535 evaluable febrile episodes in neutropenic patients were randomly assigned to treatment with ticarcillin-clavulanate plus vancomycin (TV), ceftazidime plus vancomycin (CV), or all three antibiotics (TCV). The TCV regimen was significantly more effective than TV, considering all evaluable episodes, documented infections, gram-negative infections, and infections in patients with persistent severe neutropenia (less than 100 neutrophils/mm3). The results with CV were intermediate between TV and TCV. The toxicities were similar with all three regimens and consisted primarily of skin rashes. The TCV regimen is effective for empiric therapy of fever in neutropenic patients and probably should be utilized in preference to CV or TV, although its superiority over CV in this study was inconclusive.
- Published
- 1990
- Full Text
- View/download PDF
32. Lethal and cytokinetic effects of anguidine on a human colon cancer cell line.
- Author
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Dosik GM, Barlogie B, Johnston DA, Murphy WK, and Drewinko B
- Subjects
- Adenocarcinoma pathology, Cell Cycle drug effects, Cell Line, Cell Survival drug effects, Colonic Neoplasms pathology, Humans, Kinetics, Neoplasms, Experimental drug therapy, Trichothecenes administration & dosage, Adenocarcinoma drug therapy, Colonic Neoplasms drug therapy, Sesquiterpenes pharmacology, Trichothecenes pharmacology
- Abstract
Anguidine is a fungal metabolite with antitumor activity in a murine colon cancer model. Because of disappointing results in clinical trials, we analyzed the lethal and cytokinetic effects of anguidine on cultured human colon cancer cells. The studies revealed a moderate reduction in survival only after prolonged drug exposure. Continuous incubation with anguidine for longer than 48 hr produced a moderate increase in the percentage of S-phase cells and a slight decrease in the proportion of cells in G1/0, by pulse cytophotometry. An immediate reduction in the cumulative labeling index for cells continuously exposed to tritiated thymidine and anguidine and a rapid decrease in the cumulative mitotic index for cells continuously exposed to Colcemid and anguidine indicated a block at the G1 into S and G2 into mitosis transitions. Tumoricidal activity of anguidine in a cultured human colon cancer line is poor and requires prolonged exposure. The kinetic data reflect an almost frozen state of the cell cycle.
- Published
- 1978
33. Chemoimmunotherapy of disseminated malignant melanoma with DTIC-BCG, transfer factor + melphalan.
- Author
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Schwarz MA, Gutterman JU, Burgess MA, Heilbrun LK, Murphy WK, Bodey GP, Stone E, Turner-Chism V, and Hersh EM
- Subjects
- Adult, Aged, Blood Cell Count, Drug Therapy, Combination, Female, Humans, Immunocompetence drug effects, Immunotherapy, Male, Melanoma immunology, Middle Aged, Neoplasm Metastasis, Prognosis, Skin Tests, Time Factors, BCG Vaccine administration & dosage, Dacarbazine administration & dosage, Melanoma therapy, Melphalan administration & dosage, Transfer Factor administration & dosage
- Abstract
The experimental synergism of melphalan with DTIC and the ability of transfer factor to improve immunocompetence were the basis of an attempt to improve therapeutic results in disseminated malignant melanoma. Sixty-four evaluable patients with disseminated malignant melanoma were treated in a 21-day cycle as follows: DTIC 250 mg/M2 intravenously days 1 to 5, Connaught BCG 6 X 10(8) organisms on days 7, 12, and 17 by scarification, and transfer factor 1 unit (10(9) lymphocytes equivalent, from immunocompetent relatives of patients) subcutaneously on day 12, with or without L-PAM 30 mg/M2 on day 1. Twenty-nine patients received L-PAM and 35 did not. Remission rates of 17% and 23%, respectively, occurred in these groups. An additional 15 patients received DTIC-BCG and three doses of transfer factor on days 7, 12, and 17 and had a remission rate of 20%. Remission duration and survival were compared to historical controls of 111 patients treated with DTIC and 89 treated with DTIC-BCG. Median survival on DTIC-BCG-Transfer Factor was seven months compared to four months for DTIC (P = .003) but did not differ from DTIC-BCG. Addition of L-PAM did not improve remission duration or survival compared to DTIC-BCG but enhanced myelosuppression and immunosuppression. A 60% increase in delayed type hypersensitivity to recall antigens occurred in this study compared to 34% with DTIC-BCG (P = .005). Prognosis and immunocompetence were not directly related. In summary, in this study, (1) transfer factor therapy did not enhance the clinical effects of DTIC-BCG, although it augmented delayed type hypersensitivity to recall antigens; and (2) L-PAM was not additive to DTIC in the treatment of disseminated malignant melanoma and may have abrogated the effect of immunotherapy.
- Published
- 1980
- Full Text
- View/download PDF
34. Clinical phase I-II study of cis-dichloro-diammineplatinum(II) given by continuous lv infusion.
- Author
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Salem P, Hall SW, Benjamin RS, Murphy WK, Wharton JT, and Bodey GP
- Subjects
- Cisplatin adverse effects, Cisplatin therapeutic use, Clinical Trials as Topic, Drug Evaluation, Female, Humans, Infusions, Parenteral, Cisplatin administration & dosage, Neoplasms drug therapy
- Abstract
To determine the efficacy and toxicity of cis-dichlorodiammineplatinum(II) (DDP) by a continuous iv infusion (CIVI) schedule, 34 patients with a variety of solid tumors were studied. All patients were refractory to prior chemotherapy and received a loading dose of 5 mg/m2 of DDP iv followed by 20 mg/m2 by CIVI daily for 5 days. In 25 evaluable patients, there were four (16%) complete or partial responders, nine (25%) with stable disease, and 12 (48%) with tumor progression. One complete and one partial remission were seen in two patients with disseminated basal cell carcinoma, with partial responses also seen in cervical and head and neck squamous cancer. Patients experienced renal damage (21%) and audiotoxicity (10%). Nausea and vomiting was severe in only 6%. DDP by CIVI appears to have comparable toxicity to DDP administered by other schedules; however, the diminished gastrointestinal toxicity makes the drug better tolerated by patients for whom the inconvenience of a 5-day hospitalization is less than that caused by the nausea and vomiting of rapid infusion programs.
- Published
- 1978
35. Phase II evaluation of AMSA in adult sarcomas.
- Author
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Yap BS, Plager C, Benjamin RS, Murphy WK, Legha SS, and Bodey GP
- Subjects
- Adolescent, Adult, Aged, Aminoacridines adverse effects, Amsacrine, Antineoplastic Agents therapeutic use, Blood Cell Count drug effects, Dose-Response Relationship, Drug, Drug Evaluation, Female, Histiocytoma, Benign Fibrous drug therapy, Histiocytoma, Benign Fibrous pathology, Humans, Male, Middle Aged, Nausea chemically induced, Prognosis, Sarcoma pathology, Vomiting chemically induced, Aminoacridines therapeutic use, Sarcoma drug therapy
- Abstract
AMSA an acridine derivative, was administered to 35 adults with previously treated advanced sarcomas. Patients with adequate bone marrow reserve received 120-150 mg/m2 of AMSA as a single dose repeated every 3 weeks. Patients with inadequate bone marrow reserve received 100-120 mg/m2 of AMSA. Among 31 evaluable patients, there was one partial response that lasted 6 months in a patient with intra-abdominal malignant fibrous histiocytoma with liver metastases. Thirteen patients had stable disease with a median time to disease progression of 5 months (range, 2-13), while 17 patients demonstrated progressive disease with a median time to disease progression of 2 months (range, 1-3). The median survival time for the 31 evaluable patients in this study was 5 months. The toxic effects were mild and included myelosuppression, nausea and vomiting, fever of unknown origin, and fatigue. At the dose and schedule used in this study, AMSA does not appear to have any significant activity in advanced sarcomas of adults.
- Published
- 1981
36. Role of elective brain irradiation during combined chemoradiotherapy for limited disease non-small cell lung cancer.
- Author
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Umsawasdi T, Valdivieso M, Chen TT, Barkley HT Jr, Booser DJ, Chiuten DF, Dhingra HM, Murphy WK, Dixon CL, and Farha P
- Subjects
- Antineoplastic Combined Chemotherapy Protocols, Brain Neoplasms radiotherapy, Cisplatin administration & dosage, Clinical Trials as Topic, Combined Modality Therapy, Cyclophosphamide administration & dosage, Doxorubicin administration & dosage, Female, Humans, Male, Middle Aged, Prospective Studies, Random Allocation, Brain Neoplasms secondary, Lung Neoplasms therapy
- Abstract
We have studied the clinical impact of elective brain irradiation (EBI) in patients with locally advanced, non-small cell lung cancer (LA-NSC). All patients received combination chemotherapy (cyclophosphamide + doxorubicin (Adriamycin) + cisplatin = CAP) or CAP plus radiotherapy as the initial treatment for their active tumor or as an adjuvant therapy. Of 97 evaluable patients, 46 were randomized to receive EBI (3 000 rad in 10 fractions given over two weeks). The characteristics of both groups were comparable by sex, age, performance status, pretherapy weight loss, histologic cell type, clinical staging, and type of prior therapy. EBI significantly decreased the incidence of central nervous system (CNS) metastasis in the treated group compared to the control group (4% vs 27%, p = .002). CNS involvement occurred in the treated group after failure at other sites whereas 12 of 14 control patients had CNS metastases as the first site of relapse. EBI decreased the incidence of CNS metastasis in all prognostic categories. Using multivariate analysis, the beneficial effect was shown to be significant in females, patients with good performance status, weight loss less than 6%, squamous cell histology, state III disease or no prior therapy. EBI significantly increased CNS metastasis-free interval with a beneficial effect that was significant in males, patients with weight loss less than 6%, squamous cell histology or responders. Although no survival benefit was observed for the treated group because of the adverse effect from other relapses, EBI will become more important as better treatment programs are developed.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1984
- Full Text
- View/download PDF
37. Phase II study of anguidine in advanced breast cancer.
- Author
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Yap HY, Murphy WK, DiStefano A, Blumenschein GR, and Bodey GP
- Subjects
- Adult, Aged, Antineoplastic Agents, Phytogenic adverse effects, Breast Neoplasms pathology, Female, Fusarium, Humans, Middle Aged, Trichothecenes adverse effects, Antineoplastic Agents, Phytogenic therapeutic use, Breast Neoplasms drug therapy, Sesquiterpenes therapeutic use, Trichothecenes therapeutic use
- Abstract
A phase II evaluation of anguidine was carried out in 30 patients with advanced refractory breast cancer. A dose of 5.0 mg/m2 daily for 5 days was explored. The main toxic effects were nausea and vomiting, fever and chills, hypotension, skin erythema, somnolence, confusion, and lethargy. Myelosuppression was minimal. Among these extensively pretreated patients, there was one partial responder and one additional patient who showed improvement (less than a partial response); both responses occurred in soft tissue sites.
- Published
- 1979
38. Combined chemoradiotherapy in limited-disease, inoperable non-small cell lung cancer.
- Author
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Umsawasdi T, Valdivieso M, Barkley HT Jr, Chen T, Booser DJ, Chiuten DF, Dhingra HM, Murphy WK, and Carr DT
- Subjects
- Antineoplastic Combined Chemotherapy Protocols adverse effects, Cisplatin administration & dosage, Combined Modality Therapy, Doxorubicin administration & dosage, Humans, Lung Neoplasms drug therapy, Lung Neoplasms pathology, Lung Neoplasms radiotherapy, Male, Neoplasm Staging, Phosphoramide Mustards administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Lung Neoplasms therapy
- Abstract
Forty-three patients with limited-disease, inoperable non-small cell lung cancer received two intravenous courses of cyclophosphamide, Adriamycin, and cisplatin (CAP) chemotherapy over a 6-week period. This was followed by 5 weeks of combined chemoradiotherapy (CCRT) consisting of low weekly doses of CAP for 5 weeks plus 50 Gy continuous X ray therapy (XRT) to the primary tumor site. Chemotherapy was continued until disease progression occurred or until the total dose of Adriamycin reached 450 mg/m2, whichever came first. CCRT improved the response rate [complete response (CR) plus partial responses (PR)] from 25% after two courses of CAP alone to 65% after CCRT. Previous response to two courses of CAP influences response subsequent to CAP plus XRT. A pretherapy weight loss of 6% or greater had a significant adverse effect on both response and survival time. The median survival time for all patients was 50 weeks; patients whose disease responded to treatment survived significantly longer than patients with nonresponding disease. The median time until disease progression was 37 weeks. Twenty-seven patients relapsed. The first sites of relapse were local in 30% of the patients, distant in 56% of them, and both local and distant in 15%. Severe esophagitis occurred in 30% of the patients and was dose-limiting. The administration of CCRT resulted in an improved response rate compared with the rates reported in previous studies of chemotherapy or radiotherapy alone. Further improvement of the CCRT program is needed to increase long-term survival time and to decrease esophageal toxicity.
- Published
- 1988
- Full Text
- View/download PDF
39. Serial labeling index determination as a predictor of response in human solid tumors.
- Author
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Murphy WK, Livingston RB, Ruiz VG, Gercovich FG, George SL, Hart JS, and Freireich EJ
- Subjects
- Antineoplastic Agents therapeutic use, Biopsy, Bone Marrow pathology, Bone Marrow Cells, Cell Count, Cell Division, Cytodiagnosis methods, Evaluation Studies as Topic, Exudates and Transudates, Humans, Neoplasms diagnosis, Neoplasms drug therapy, Cytological Techniques, Neoplasms pathology
- Abstract
A rapid method for determining labeling indices in solid tumor specimens, tumor-induced effusions, and tumor-bearing bone marrows was utilized in 116 patients. Of these, 48 patients were studied pre- and postchemotherapy. The magnitude of a significant change in labeling index (LI percent) was determined statistically. Of the 48 patients studied serially, 42 were studied 17 days or less following completion of their chemotherapy. In 26 patients without a significant change in tumor LI percent, there was no subsequent clinical response to chemotherapy. Three additional patients in this group are inevaluable at present. In 11 patients, there was a significant fall in tumor LI percent following chemotherapy. Seven of these had a 50 percent or greater regression of demonstrable disease, one patient had definite tumor effect but the effect was not a partial response and three patients were not evaluable for clinical response. In two patients there was a significant increase in tumor LI percent and the patients had rapid tumor progression and death. Predictions derived from serial study of the LI percent by this method correlate significantly with subsequent behavior of the tumors tested following chemotherapy and may prove clinically useful in making decisions about when or whether to change therapy.
- Published
- 1975
40. High-dose intensification therapy with autologous bone marrow support for limited small-cell bronchogenic carcinoma.
- Author
-
Spitzer G, Farha P, Valdivieso M, Dicke K, Zander A, Vellekoop L, Murphy WK, Dhingra HM, Umsawasdi T, and Chiuten D
- Subjects
- Adult, Aged, Carcinoma, Bronchogenic drug therapy, Clinical Trials as Topic, Combined Modality Therapy, Cyclophosphamide administration & dosage, Doxorubicin administration & dosage, Etoposide administration & dosage, Female, Follow-Up Studies, Humans, Ifosfamide administration & dosage, Lung Neoplasms drug therapy, Male, Middle Aged, Transplantation, Autologous, Vincristine administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bone Marrow Transplantation, Carcinoma, Bronchogenic therapy, Lung Neoplasms therapy
- Abstract
The efficacy and toxicity of high-dose chemotherapy with autologous bone marrow transplantation (ABMT) was studied in 32 patients with untreated limited small-cell bronchogenic carcinoma (SCBC). Ten patients received three courses of induction therapy consisting of vincristine (VCR) (1.5 mg X 2), ifosfamide (5 g/m2), and Adriamycin (Ad; Adria Laboratories, Columbus, Ohio) (60 mg/m2). Patients then received two courses of intensification therapy with cyclophosphamide (CYT) (4.5 g/m2), 4' demethyl-epipodophyllotoxin-d-D-ethylidene glucoside (VP-16-213) (600 mg/m2) and VCR (2 mg) with ABMT. Another 22 patients received induction therapy with VCR, CYT (600 mg/m2), Ad (50 mg/m2), and VP-16-213 (180 mg/m2). All 22 patients also received intensification therapy of the same dose of CYT (4.5 g/m2) and VP-16-213 (600 mg/m2). Nine patients also received high-dose methotrexate (MTX), four patients received Ad (40 to 60 mg/m2), and two patients received both Ad and MTX. After intensification, patients received elective prophylactic brain irradiation (3,000 rad) and chest irradiation (5,000 rad). After induction therapy, there were 13 (41%) complete remissions (CR) and 17 (53%) partial remissions (PR). After intensification therapy, there were 22 CRs (69%) and 10 PRs (31%). Median survival for all patients was 14 months (range, 5 to 59+). Of the 13 patients who received intensification therapy in CR, five remain disease free (DF), four for 4 years or longer. Of the nine patients to achieve CR with intensification, only one is DF. No patient died during intensification. In conclusion, intensification with high-dose chemotherapy can increase the CR rate, and this approach is most likely to show long-term benefits in patients with minimal disease (CR) at the beginning of intensification therapy.
- Published
- 1986
- Full Text
- View/download PDF
41. Phase II study of tiazofurin (NSC 286193) in the treatment of advanced small cell bronchogenic carcinoma.
- Author
-
Holoye PY, Carr DT, Dhingra HM, Glisson BS, Lee JS, Murphy WK, Umsawasdi T, and Jeffries D
- Subjects
- Adult, Aged, Drug Evaluation, Female, Humans, Male, Middle Aged, Ribavirin adverse effects, Ribavirin analogs & derivatives, Antineoplastic Agents therapeutic use, Carcinoma, Bronchogenic drug therapy, Carcinoma, Small Cell drug therapy, Lung Neoplasms drug therapy, Ribavirin therapeutic use, Ribonucleosides therapeutic use
- Abstract
Fourteen evaluable patients with small cell bronchogenic carcinoma received tiazofurin, an inhibitor of inosine monophosphate dehydrogenase, that progressed after one combination chemotherapy. No objective remission was observed at the dosage of 800 mg/m2 for 5 consecutive days. Toxicity was moderate.
- Published
- 1988
- Full Text
- View/download PDF
42. Phase I clinical evaluation of 2,3-dihydro-1H-imidazo[1,2-b]pyrazole.
- Author
-
Yap BS, Murphy WK, Burgess MA, Valdivieso M, and Bodey GP
- Subjects
- Adult, Aged, Anemia, Hemolytic chemically induced, Antineoplastic Agents administration & dosage, Antineoplastic Agents toxicity, Bone Marrow drug effects, Drug Evaluation, Female, Hemolysis drug effects, Humans, Imidazoles administration & dosage, Imidazoles therapeutic use, Imidazoles toxicity, Male, Middle Aged, Pyrazoles administration & dosage, Pyrazoles toxicity, Antineoplastic Agents therapeutic use, Neoplasms drug therapy, Pyrazoles therapeutic use
- Abstract
2,3-Dihydro-1H-imidazo[1,2-b]pyrazole, a DNA synthesis inhibitor, was given to 25 patients in a phase I study. The drug was administered by rapid iv infusion daily x 5 days at 3-week intervals at doses ranging from 150 to 1500 mg/m2/day. Side effects were observed with doses of greater than or equal to 1000 mg/m2/day and included nausea and vomiting, diarrhea, dark urine, and anemia. At doses of 1500 mg/m2, three patients had evidence of hemolysis (two had hemoglobinuria and one had acute intravascular hemolysis). The hemolysis was severe enough to cause death in one patient and necessitated abandoning further dose escalation. There was minimal or no myelosuppression at any dose level. No objective tumor regression was observed in any of the 16 patients evaluable for response. Further studies are recommended to carefully evaluate the etiology of the hemolysis before proceeding to a phase II trial. It is unlikely that this drug will prove to be useful unless methods for circumventing hemolysis are developed.
- Published
- 1979
43. Neoplasia, kinetics, nd chemotherapy.
- Author
-
Hart JS, Livingston RB, Murphy WK, Barlogie B, Gehan EA, and Bodey GP
- Subjects
- Acute Disease, Animals, Cell Survival, Chick Embryo, Culture Techniques, Dose-Response Relationship, Drug, Drug Evaluation, Drug Evaluation, Preclinical, Humans, Leukemia drug therapy, Leukemia L1210 drug therapy, Neoplasms, Experimental drug therapy, Remission, Spontaneous, Antineoplastic Agents therapeutic use, Cell Division drug effects, Neoplasms drug therapy
- Published
- 1976
44. I.v. melphalan in carcinoma of the lung: effect of cyclophosphamide priming on hematopoietic toxicity.
- Author
-
Spitzer G, Valdivieso M, Farha P, Murphy WK, Dhingra HM, Chiuten D, Umsawasdi T, and Holoye P
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Carcinoma, Bronchogenic pathology, Cyclophosphamide administration & dosage, Female, Hematologic Diseases chemically induced, Humans, Leukocyte Count, Lung Neoplasms pathology, Male, Melphalan administration & dosage, Middle Aged, Nausea chemically induced, Neutrophils, Platelet Count, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Bronchogenic drug therapy, Lung Neoplasms drug therapy, Melphalan therapeutic use
- Abstract
Thirty-six patients with lung cancer, 24 with prior chemotherapy and 12 without prior chemotherapy, received iv melphalan at doses ranging from 20 to 40 mg/m2 of body surface area. Patients who showed moderate myelosuppression and remained in the study were also investigated to determine if cyclophosphamide (300 mg/m2) administered 1 week before the identical dose of i.v. melphalan modified the hematopoietic toxicity of melphalan (cyclophosphamide priming). In this study, the activity of melphalan was minimal, four minor responses with no partial or complete responses. Three of these minor responses were in previously untreated patients. The major toxicity was hematopoietic and the maximum tolerated i.v. dose was 20 mg/m2 in the patients previously treated with chemotherapy and 30 mg/m2 in those without prior chemotherapy. Cyclophosphamide priming did not reduce the myeloid toxicity. Myelosuppression was more severe in the course that included cyclophosphamide. Recovery, however, appeared to be similar in both courses. I.v. melphalan at these doses has minimal activity in lung cancer. Cyclophosphamide administered 1 week before i.v. melphalan does not decrease the myelosuppression but should be investigated further for its effect on the rate of wbc and neutrophil count recovery.
- Published
- 1986
45. The natural history of resectable metastatic melanoma (Stage IVA melanoma).
- Author
-
Feun LG, Gutterman J, Burgess MA, Hersh EM, Mavligit G, McBride CM, Benjamin RS, Richman SP, Murphy WK, Bodey GP, Brown BW, Mountain CF, Leavens ME, and Freireich EJ
- Subjects
- Adolescent, Adult, Aged, Antineoplastic Agents therapeutic use, Bacterial Vaccines therapeutic use, Female, Humans, Male, Melanoma surgery, Middle Aged, Neoplasm Metastasis, Prognosis, Propionibacterium acnes immunology, Skin Neoplasms surgery, Skin Neoplasms therapy, Melanoma pathology, Skin Neoplasms pathology
- Abstract
One-hundred-two patients with malignant melanoma who had distant metastases surgically resected and were judged to be clinically free of disease (M. D. Anderson Stage IVA melanoma) were studied. The median survival for all the patients from time of diagnosis of stage IVA disease was 18 months. The site of the resected metastases did not appear to influence survival, being approximately the same for the brain (15 months), lung (16 months), intraabdominal (18 months), and skin and/or lymph nodes (23 months). The site of the resected metastases also did not influence the median disease-free interval. Patients who had metastases resected from several organs at the same time had a median survival of 15 months, which was similar to that of patients with one resected site. Patients who were rendered Stage IVA on several occasions by surgical excisions had a median survival of 36 months. Thirty-five patients received surgery only and 67 patients received adjuvant chemotherapy, immunotherapy, or combined chemoimmunotherapy after surgery. For the group treated with surgery only, the median disease-free interval and survival from diagnosis of stage IVA disease were 6 months and 16 months, respectively, and for the adjuvant group 6 months and 21 months, respectively. Specifically, by the type of adjuvant therapy, the median disease-free interval and survival from stage IVA for 23 patients receiving Corynebacterium parvum were 6.9 and 19 months; for 39 patients receiving BCG, eight months and 26 months; for 24 patients receiving BCG + DTIC, eight and 17.4 months; and for all 51 DTIC treated patients 6.3 and 17.8 months, respectively. Patients receiving BCG had a median survival superior to the surgery only group (P = 0.02). An increase in survival was seen predominantly in patients who achieved IVA status more than once and received BCG. Patients with recurrent soft-tissue metastases appeared to benefit most from BCG in prolonging the disease-free interval. Only 1/10 treated by surgery alone had a disease-free interval longer than 1 year, compared with 9/16 who received BCG (P = 0.01). Stage IVA melanoma appears to be distinctly different in prognosis from Stage IVB melanoma and should be classified separately. Patients with recurrent soft-tissue disease may benefit significantly from treatment with BCG.
- Published
- 1982
- Full Text
- View/download PDF
46. GR 38032F (GR-C507/75): a novel compound effective in the prevention of acute cisplatin-induced emesis.
- Author
-
Hesketh PJ, Murphy WK, Lester EP, Gandara DR, Khojasteh A, Tapazoglou E, Sartiano GP, White DR, Werner K, and Chubb JM
- Subjects
- Acute Disease, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Female, Humans, Imidazoles administration & dosage, Male, Middle Aged, Multicenter Studies as Topic, Nausea chemically induced, Ondansetron, Random Allocation, Vomiting chemically induced, Cisplatin adverse effects, Imidazoles therapeutic use, Nausea prevention & control, Serotonin Antagonists, Vomiting prevention & control
- Abstract
We evaluated, in a multi-center trial, the safety and efficacy of GR 38032F (GR-C507/75), a novel and selective serotonin antagonist, in preventing acute emesis in chemotherapy-naive patients receiving treatment with regimens containing high-dose cisplatin (greater than or equal to 100 mg/m2). Eighty-five patients were randomized to receive GR 38032F, 0.18 mg/kg, either every six or every eight hours for three doses, beginning 30 minutes before cisplatin. Patients were evaluated for emetic episodes (vomiting or retching) over a 24-hour period following cisplatin. All patients were evaluable for toxicity and 83 were evaluable for efficacy. The overall antiemetic response rate was 75% (55% complete response [CR], 20% major response). No difference in antiemetic control between the two administration schedules was noted. Patients with histories of heavy ethanol use had significantly better antiemetic control (74% CR) than modest or non-drinkers (33% CR). Toxicity of GR 38032F was modest and independent of administration schedule. The most common adverse events included mild hepatic transaminase elevations, self-limited diarrhea, dry mouth, headache, and mild sedation. Our data indicate that GR 38032F is a safe and effective agent in the control of acute cisplatin-induced nausea and vomiting. Additional trials exploring dosing, schedule, and comparison to standard antiemetic agents are indicated.
- Published
- 1989
- Full Text
- View/download PDF
47. A rapid in vitro labeling index method for predicting response of human solid tumors to chemotherapy.
- Author
-
Thirlwell MP, Livingston RB, Murphy WK, and Hart JS
- Subjects
- Autoradiography methods, Breast Neoplasms blood, Breast Neoplasms drug therapy, Breast Neoplasms metabolism, Female, Humans, In Vitro Techniques, Male, Melanoma blood, Melanoma drug therapy, Melanoma metabolism, Neoplasms blood, Neoplasms metabolism, Thymidine metabolism, Antineoplastic Agents therapeutic use, Drug Evaluation methods, Neoplasms drug therapy
- Abstract
A rapid autoradiographic technique for measuring the [3H]thymidine-labeling index of human solid tumors has been adapted to assess the effect of anticancer drugs in vitro. The drugs tested were present unchanged or as metabolites in serum obtained from patients immediately post-treatment. In 15 patients, the drugs tested in vitro were also given in vivo. Tumor-labeling index fell significantly in 5 of 6 patients who were later found to have objective clinical response. Tumor-labeling index did not change significantly in 8 patients and rose significantly in 1 of 9 patients who lacked clinical response. If confirmed, this in vitro test may prove to be a useful method of predicting responsiveness of human solid cancers to chemotherapeutic agents.
- Published
- 1976
48. Protected environment - prophylactic antibiotic program for malignant sarcomas: randomized trial during remission induction chemotherapy.
- Author
-
Bodey GP, Rodriguez V, Murphy WK, Burgess A, and Benjamin RS
- Subjects
- Adolescent, Adult, Aged, Cyclophosphamide administration & dosage, Dacarbazine administration & dosage, Doxorubicin administration & dosage, Drug Administration Schedule, Drug Therapy, Combination, Humans, Middle Aged, Probability, Prognosis, Random Allocation, Sarcoma prevention & control, Vincristine administration & dosage, Antineoplastic Agents administration & dosage, Sarcoma drug therapy
- Abstract
Fifty-one valuable patients with malignant sarcomas were randomly allocated to receive three courses of remission induction chemotherapy with cyclophosphamide, vincristine, Adriamycin, and dimethyl triazeno imidazole carboxamide (CYVADIC) on the protected environment-prophylactic antibiotic for the control group (P = 0.22). The response rates (complete plus partial) were 71% and 67%, respectively. The durations of response were similar for both groups of patients, but the PEPA patients survived substantially longer (median, 84 weeks vs. 58 weeks). The frequency of infection was significantly lower among the PEPA patients, and the doses of CYVADIC could be escalated more often among these patients. Dosage escalation was associated with a higher complete remission rate and lower fatality rate.
- Published
- 1981
- Full Text
- View/download PDF
49. Neurotoxicity in long-term survivors of small cell lung cancer.
- Author
-
Lee JS, Umsawasdi T, Lee YY, Barkley HT Jr, Murphy WK, Welch S, and Valdivieso M
- Subjects
- Brain drug effects, Brain radiation effects, Brain Neoplasms prevention & control, Brain Neoplasms secondary, Combined Modality Therapy, Female, Lung Neoplasms drug therapy, Lung Neoplasms radiotherapy, Male, Retrospective Studies, Antineoplastic Combined Chemotherapy Protocols adverse effects, Brain Diseases etiology, Carcinoma, Small Cell therapy, Lung Neoplasms therapy, Radiotherapy adverse effects
- Abstract
Chronic central nervous system neurotoxicity was studied in 38 long-term survivors (greater than or equal to 3 years) of small cell lung cancer who were treated at the University of Texas M. D. Anderson Hospital and Tumor Institute at Houston between 1971 and 1980. All but one patient received combination chemotherapy with or without chest irradiation. Twenty-four patients received whole brain irradiation (Group I), 22 for "elective" and two for therapeutic purposes, while 14 did not (Group II). Abnormalities in computed tomographic (CT) scans of the brain were more frequently observed in Group I than in Group II (70% vs. 0%, p less than 0.01). Clinical central nervous system neurotoxicity developed in three patients in Group I, while none developed in patients in Group II (p less than 0.05). Patients who received methotrexate and procarbazine after whole brain irradiation were at a higher risk for clinical central nervous system neurotoxicity (p less than 0.05), and for development of periventricular white matter changes in CT brain scans (p less than 0.05) than were patients in Group II. Impaired methylation of the myelin sheath is proposed as a possible underlying pathogenic mechanism.
- Published
- 1986
- Full Text
- View/download PDF
50. Effects of intensive induction chemotherapy for extensive-disease small cell bronchogenic carcinoma in protected environment-prophylactic antibiotic units.
- Author
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Valdivieso M, Cabanillas F, Keating M, Barkley HT, Murphy WK, Burgess MA, Frazier H, Chen T, and Bodey GP
- Subjects
- Adult, Aged, Bacterial Infections complications, Cyclophosphamide administration & dosage, Doxorubicin administration & dosage, Etoposide administration & dosage, Female, Humans, Ifosfamide administration & dosage, Leukocyte Count, Lung Neoplasms secondary, Male, Mediastinal Neoplasms secondary, Methotrexate administration & dosage, Middle Aged, Procarbazine administration & dosage, Vincristine administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Bronchogenic drug therapy, Carcinoma, Small Cell drug therapy, Environment, Controlled, Lung Neoplasms drug therapy
- Abstract
Fifty-five patients with extensive-disease small cell bronchogenic carcinoma received three courses of intensive, inpatient, remission induction chemotherapy in (25 patients) or out (30 patients) of protected environment-prophylactic antibiotic (PEPA) units. Chemotherapy consisted of ECHO induction (E = epipodophyllotoxin VP-16-213; C = cyclophosphamide; H = hydroxydaunorubicin; O = Oncovin) and PRIME maintenance (PR = procarbazine; I = ifosfamide; ME = methotrexate). All evaluable patients (22 in the protected environment group and 26 in the control group) had a complete (50 percent in the protected environment group and 54 percent in the control group) or partial (50 percent in the protected environment group and 46 percent in the control group) remission. Median response and survival durations for both treatment groups were similar. The median survival duration of patients with a complete remission favored the protected environment group (16.5 versus 12.67 months; p = 0.20). Two patients (one from each group) are alive and disease-free for more than four years. Myelosuppression was intense and more pronounced in the protected environment group (p less than or equal to 0.01). Infectious complications were less common in patients receiving intravenous prophylactic antibiotics and in those treated with intravenous antibiotics in PEPA units (p less than or equal to 0.04). There were no treatment-related deaths, although treatment might have contributed to the death of three patients in the protected environment group and four in the control group. The administration of intensive ECHO induction chemotherapy to patients with extensive small cell bronchogenic carcinoma produced a high complete remission rate, although there was no significant long-term survival advantage over a program of less intensity. The administration of intravenous prophylactic antibiotics and the use of PEPA units significantly reduced the infectious morbidity of chemotherapy.
- Published
- 1984
- Full Text
- View/download PDF
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