8 results on '"Hudes G"'
Search Results
2. Phase II study to assess the efficacy, safety and tolerability of the mitotic spindle kinesin inhibitor AZD4877 in patients with recurrent advanced urothelial cancer.
- Author
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Jones R, Vuky J, Elliott T, Mead G, Arranz JA, Chester J, Chowdhury S, Dudek AZ, Müller-Mattheis V, Grimm MO, Gschwend JE, Wülfing C, Albers P, Li J, Osmukhina A, Skolnik J, and Hudes G
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- Adult, Aged, Aged, 80 and over, Antineoplastic Agents adverse effects, Antineoplastic Agents pharmacokinetics, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use, Benzamides pharmacokinetics, Benzamides pharmacology, Demography, Female, Humans, Kinesins metabolism, Male, Middle Aged, Neoplasm Recurrence, Local pathology, Neoplasm Staging, Pyrimidinones pharmacokinetics, Pyrimidinones pharmacology, Spindle Apparatus drug effects, Treatment Outcome, Urinary Bladder Neoplasms pathology, Benzamides adverse effects, Benzamides therapeutic use, Kinesins antagonists & inhibitors, Neoplasm Recurrence, Local drug therapy, Pyrimidinones adverse effects, Pyrimidinones therapeutic use, Spindle Apparatus metabolism, Urinary Bladder Neoplasms drug therapy, Urothelium pathology
- Abstract
Background: AZD4877 is a potent inhibitor of the mitotic spindle kinesin, Eg5. Early-phase clinical studies in a broad range of cancers showed that AZD4877 is well tolerated. This Phase II study evaluated the efficacy, safety and pharmacokinetics (Cmax) of AZD4877 in patients with previously treated advanced urothelial cancer (ClinicalTrials.gov identifier NCT00661609)., Patients and Methods: AZD4877 25 mg was administered once-weekly for 3 weeks of each 4-week cycle until disease progression, death, unacceptable toxicity or withdrawal. The primary objective was to determine the objective response rate (RECIST). Recruitment was to be halted if ≤ 2 of the first 20 evaluable patients achieved an objective tumor response. Cmax was assessed on days 1 and 8 of cycle 1., Results: None of the first 20 patients evaluable for efficacy achieved an objective response; enrollment was therefore halted. During this initial analysis, a further 21 patients were recruited. Overall, 39 patients were evaluable for efficacy, including one with confirmed partial response (PR) and seven patients with stable disease for ≥ 8 weeks (including one unconfirmed PR). The most commonly reported treatment-related adverse events (TRAEs) were neutropenia (22 patients), fatigue (12), leukopenia (7) and constipation (6); the most commonly reported grade ≥ 3 TRAE was neutropenia (21). Four patients had serious TRAEs. On days 1 and 8, the geometric mean Cmax of AZD4877 was 138 ng/ml (CV = 75 %) and 144 ng/ml (CV = 109 %), respectively., Conclusions: AZD4877 was generally tolerable in patients with advanced urothelial cancer. Given the limited clinical efficacy, further development of AZD4877 in urothelial cancer is not planned.
- Published
- 2013
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- View/download PDF
3. A phase 1 study of a chimeric monoclonal antibody against interleukin-6, siltuximab, combined with docetaxel in patients with metastatic castration-resistant prostate cancer.
- Author
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Hudes G, Tagawa ST, Whang YE, Qi M, Qin X, Puchalski TA, Reddy M, Cornfeld M, and Eisenberger M
- Subjects
- Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal administration & dosage, Antibodies, Monoclonal adverse effects, Antibodies, Monoclonal pharmacokinetics, Antineoplastic Agents administration & dosage, Antineoplastic Agents adverse effects, Antineoplastic Agents pharmacokinetics, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols pharmacokinetics, C-Reactive Protein analysis, Docetaxel, Humans, Interleukin-6 immunology, Male, Middle Aged, Neoplasm Metastasis, Orchiectomy, Prostate-Specific Antigen blood, Prostatic Neoplasms blood, Prostatic Neoplasms pathology, Taxoids administration & dosage, Taxoids adverse effects, Taxoids pharmacokinetics, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Prostatic Neoplasms drug therapy
- Abstract
Purpose: Siltuximab is a chimeric, anti-interleukin-6 monoclonal antibody with potential therapeutic benefit in castration-resistant prostate cancer (CRPC) patients. We assessed the safety and tolerability of siltuximab in combination with docetaxel, the pharmacokinetics of docetaxel alone and with siltuximab, and the efficacy and pharmacodynamics of siltuximab plus docetaxel., Patients and Methods: In an open-label, dose-escalation, multicenter, phase 1 study, patients with metastatic, progressive CRPC received docetaxel 75 mg/m(2) q3w plus siltuximab 6 mg/kg q2w (n=12), 9 mg/kg q3w (n=12), or 12 mg/kg q3w (n=15). Dose-limiting toxicity (DLT), PSA, and radiologic response according to WHO criteria were evaluated., Results: DLT was reported in 1 of 11 patients receiving 6 mg/kg, 1 of 12 receiving 9 mg/kg, and in 1 of 14 receiving 12 mg/kg. Common Grade ≥ 3 adverse events were neutropenia (73 %), leukopenia (60 %), lymphopenia (30 %), dyspnea (19 %), and fatigue (14 %). Toxicities were not dose dependent. Siltuximab did not affect docetaxel pharmacokinetics. The pharmacokinetic profile for siltuximab in combination was similar to single-agent siltuximab pharmacokinetics. Twenty-three (62 %; 95 % CI 45 %, 78 %) of 37 combination-treated patients achieved a confirmed ≥ 50 % PSA decline. Of 17 patients with measurable disease at baseline, 2 confirmed and 2 unconfirmed radiologic partial responses ranging 190 to 193 days were achieved with 9- and 12-mg/kg siltuximab. C-reactive protein concentrations were suppressed throughout treatment in all patients., Conclusion: These results suggest that siltuximab in combination with docetaxel is safe and shows preliminary efficacy in patients with CRPC, although alternative siltuximab schedules may be better tolerated for future studies.
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- 2013
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4. Phase II study of KOS-862 in patients with metastatic androgen independent prostate cancer previously treated with docetaxel.
- Author
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Beer TM, Higano CS, Saleh M, Dreicer R, Hudes G, Picus J, Rarick M, Fehrenbacher L, and Hannah AL
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- Aged, Aged, 80 and over, Antineoplastic Agents administration & dosage, Antineoplastic Agents adverse effects, Disease Progression, Docetaxel, Dose-Response Relationship, Drug, Epothilones administration & dosage, Epothilones adverse effects, Humans, Infusions, Intravenous, Male, Middle Aged, Neoplasm Metastasis, Prostate-Specific Antigen blood, Prostatic Neoplasms mortality, Prostatic Neoplasms pathology, Survival Rate, Treatment Outcome, Antineoplastic Agents therapeutic use, Epothilones therapeutic use, Prostatic Neoplasms drug therapy, Taxoids therapeutic use
- Abstract
Based on the pre-clinical spectrum of activity in taxane-resistant cell lines, we evaluated KOS-862 (epothilone D; 12,13-desoxyepothilone B) as second-line chemotherapy in androgen-independent prostate cancer.Thirty-eight men with metastatic androgen-independent prostate cancer and evidence of progression following docetaxel-based chemotherapy were treated with KOS-862, 100 mg/m(2) (maximum of 240 mg) i.v. weekly for 3 weeks, repeated every 4 weeks. The primary objective for this study was to determine the antitumor activity, measured by PSA decline by more then 50% confirmed 4 weeks later. Two patients (5.3%, 90% CI 1-16%) met criteria for confirmed PSA decline. While both of these patients had previously been treated with docetaxel, neither had confirmed docetaxel-refractory disease. None of the 24 patients with measurable disease had a confirmed partial response. Seventy-three percent of patients had an adverse event leading to dose delay, reduction, or treatment discontinuation. Neurological toxicity and fatigue predominated. Seventeen patients (44.7%) had treatment related grade 3 neurological adverse events including peripheral sensory neuropathy (n = 4, 10.5%), ataxia (n = 3, 7.9%), peripheral motor neuropathy (n = 1, 2.6%), involuntary muscle contractions (n = 1, 2.6%) and neuropathic pain (n = 1, 2.6%). One subject (2.6%) had a grade 4 treatment peripheral motor neuropathy. Further study of this dose and schedule of KOS-862 in this patient population cannot be recommended due to both lack of activity and excessive toxicity.
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- 2007
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5. Toxicity and response evaluation of the interferon inducer poly ICLC administered at low dose in advanced renal carcinoma and relapsed or refractory lymphoma: a report of two clinical trials of the Eastern Cooperative Oncology Group.
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Giantonio BJ, Hochster H, Blum R, Wiernik PH, Hudes GR, Kirkwood J, Trump D, and Oken MM
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- Adult, Aged, Carboxymethylcellulose Sodium adverse effects, Carboxymethylcellulose Sodium analogs & derivatives, Drug Administration Schedule, Drug Resistance, Neoplasm, Female, Humans, Interferon Inducers adverse effects, Male, Middle Aged, Multicenter Studies as Topic, Neoplasm Recurrence, Local, Neutropenia chemically induced, Poly I-C adverse effects, Polylysine adverse effects, Polylysine analogs & derivatives, Thrombocytopenia chemically induced, Treatment Outcome, Carboxymethylcellulose Sodium administration & dosage, Carcinoma, Renal Cell drug therapy, Interferon Inducers administration & dosage, Kidney Neoplasms drug therapy, Lymphoma drug therapy, Poly I-C administration & dosage, Polylysine administration & dosage
- Abstract
Purpose: Phase II studies were conducted to evaluate the safety and efficacy of the interferon inducer Poly ICLC at low doses in advanced renal cancer and relapsed or refractory lymphoma., Patients and Methods: Twenty-nine patients with advanced renal carcinoma and eleven patients with lymphoma were treated with poly ICLC. Patients received 0.25 mg/m2 of poly ICLC intravenously twice weekly three days apart until progression or unacceptable toxicity., Results: There were no objective responses. Six patients with renal carcinoma had stable disease as best response with one patient receiving 62 weeks of therapy. Toxicity included grade 3 anemia in 8 patients and grade 4 anemia in one patient. All patients were anemic prior to entry with a median grade 2 anemia at baseline. Grade 4 neutropenia, thrombocytopenia and injection site pain occurred in one patient each. Grade 3 fever, chills or fatigue occurred in four, three, and three patients respectively. Any grade fever occurred in 10 patients (25.6%) and any grade chills occurred in 9 patients (23.1%)., Conclusion: Poly ICLC at this dose and schedule is well tolerated in both patient populations and is inactive in renal carcinoma.
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- 2001
- Full Text
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6. Phase I trial of fluorouracil modulation by N-phosphonacetyl-L-aspartate and 6-methylmercaptopurine ribonucleoside (MMPR), and leucovorin in patients with advanced cancer.
- Author
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Hageboutros A, Hudes GR, Greene F, LaCreta FP, Brennan J, and O'Dwyer PJ
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- Adult, Aged, Antimetabolites, Antineoplastic administration & dosage, Aspartic Acid administration & dosage, Aspartic Acid pharmacology, Colorectal Neoplasms drug therapy, Drug Interactions, Female, Fluorouracil administration & dosage, Fluorouracil adverse effects, Fluorouracil pharmacokinetics, Humans, Leucovorin administration & dosage, Male, Methylthioinosine administration & dosage, Middle Aged, Phosphonoacetic Acid administration & dosage, Phosphonoacetic Acid pharmacology, Antimetabolites, Antineoplastic pharmacology, Aspartic Acid analogs & derivatives, Fluorouracil therapeutic use, Leucovorin pharmacology, Methylthioinosine pharmacology, Phosphonoacetic Acid analogs & derivatives
- Abstract
The results of several clinical trials support the hypothesis that biochemical modulation may enhance the antitumor activity of 5-Fluorouracil (5-FU). We have performed a phase I trial using a combination of three different biochemical modulators at the optimal dose established in previous clinical trials. The modulators include: phosphonacetyl-l-aspartate (PALA), which may increase 5-FU incorporation into RNA; leucovorin, which potentiates thymidylate synthase inhibition; and 6-methylmercaptopurine riboside (MMPR), which promotes the intracellular retention of fluorinated nucleotides. The treatment regimen consisted of PALA 250 mg/m2 day 1, followed 24 h later by MMPR 150 mg/m2 as an iv bolus, and the initiation of a 24-hour infusion of 5-FU along with leucovorin 50 mg/m2. This regimen was repeated weekly. Doses of 5-FU were escalated in cohorts of four or more patients from 2,000 to 2,600 mg/m2. Among 20 patients entered, the majority had colorectal cancer, and most had received prior 5-FU treatment. Toxicity was predominantly gastrointestinal, and diarrhea was dose-limiting at a 5-FU dose of 2600 mg/m2. There were three partial remissions observed, two of whom had colorectal cancer. Emerging data that casts doubt on the modulation value of PALA at this dose and schedule suggests that revision of this regimen be considered before Phase II trial.
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- 1997
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- View/download PDF
7. Phase II study of topotecan in metastatic hormone-refractory prostate cancer.
- Author
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Hudes GR, Kosierowski R, Greenberg R, Ramsey HE, Fox SC, Ozols RF, McAleer CA, and Giantonio BJ
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- Aged, Aged, 80 and over, Antineoplastic Agents therapeutic use, Camptothecin adverse effects, Camptothecin therapeutic use, Drug Resistance, Neoplasm, Humans, Male, Middle Aged, Prostatic Neoplasms pathology, Topotecan, Treatment Outcome, Antineoplastic Agents adverse effects, Camptothecin analogs & derivatives, Prostatic Neoplasms drug therapy
- Abstract
Systemic chemotherapy with currently available agents has not improved survival for patients with hormone refractory prostate cancer (HRPC), consequently, the evaluation of new agents is warranted. Topotecan is a specific inhibitor of topoisomerase I with broad antitumor activity in preclinical studies. The purpose of this phase II trial was to determine the objective response rate of topotecan administered as a 30 minute infusion for five consecutive days in men with metastatic HRPC. Thirty-four evaluable patients were treated with topotecan 1.1-1.5 mg/m2 as a 30 minute infusion daily for five days, repeated every three weeks until disease progression or unacceptable toxicity. Response was assessed with a combination of standard solid tumor response criteria and the serum prostate specific antigen (PSA) for patients with bidimensionally measurable disease, and by serial measurements of the PSA in patients with bone only (evaluable) disease. One of 13 patients (7.6%) with measurable soft tissue disease had a PR in nodal sites. Of 21 patients with only osseous metastases, 1 (4.7%) had improvement in bone scan. Six of the 34 evaluable patients (17.6%) had the serum PSA decrease by > or = 50% and 2 (5.8%) had PSA decreases of > or = 75%. Toxicity was chiefly hematologic with 66% of patients experiencing Grade 3 or 4 granulocytopenia. Thirty-nine percent of cycles required a delay to allow for hematologic recovery and ten patients required red cell transfusions. Non-hematologic toxicity, mainly nausea and alopecia, was mild. Topotecan administered at this dose and schedule has limited activity in patients with HRPC. Further trials of topo I inhibition in HRPC should utilize alternative schedules of topotecan (e.g., prolonged infusion) or other camptothecin analogs with more potent topo I inhibitory activity.
- Published
- 1995
- Full Text
- View/download PDF
8. Phase II study of amonafide (nafidamide, NSC 308847) in advanced colorectal cancer.
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O'Dwyer PJ, Paul AR, Hudes GR, Walczak J, Ozols RF, and Comis RL
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- Adenine, Antineoplastic Agents administration & dosage, Antineoplastic Agents adverse effects, Drug Evaluation, Humans, Isoquinolines adverse effects, Middle Aged, Naphthalimides, Organophosphonates, Adenocarcinoma drug therapy, Antineoplastic Agents therapeutic use, Colorectal Neoplasms drug therapy, Imides, Isoquinolines therapeutic use
- Abstract
Amonafide, a benzisoquinoline-1,3-dione with anti-tumor activity in preclinical screens, was administered to patients with recurrent or metastatic bidimensionally measurable colorectal cancer. Fourteen patients with no prior chemotherapy for advanced disease, performance status 0-1, and normal bone marrow, renal, and hepatic function were entered. Amonafide 300 mg/m2 was administered intravenously over 1 hour daily for five consecutive days; courses were repeated every three weeks. The major side effect was neutropenia: Grade 3 or 4 toxicity occurred in 5/14 patients. Other toxicities included nausea and vomiting, flulike symptoms, fever, rash and alopecia. Three patients had stable disease, but there were no responses observed. Amonafide at this dose and schedule has no activity in the treatment of colorectal cancer.
- Published
- 1991
- Full Text
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