178 results on '"Peters WP"'
Search Results
2. Cardiac sequelae of doxorubicin and paclitaxel as induction chemotherapy prior to high-dose chemotherapy and peripheral blood progenitor cell transplantation in women with high-risk primary or metastatic breast cancer
- Author
-
Klein, JL, Rey, PMaroto, Dansey, RD, Karanes, C, Du, W, Abella, E, Cassells, L, Hamm, C, Peters, WP, and Baynes, RD
- Published
- 2000
- Full Text
- View/download PDF
3. Cyclophosphamide and paclitaxel as initial or salvage regimen for the mobilization of peripheral blood progenitor cells
- Author
-
Klein, JL, Rey, PM, Dansey, R, Karanes, C, Abella, E, Cassells, L, Hamm, C, Flowers, M, Couwlier, C, Peters, WP, and Baynes, RD
- Published
- 1999
- Full Text
- View/download PDF
4. High-dose therapy with autologous hematopoietic cell support as salvage treatment for patients with breast cancer who have relapsed after previous high-dose chemotherapy
- Author
-
Bearman, SI, Vredenburgh, JJ, Cagnoni, PJ, Shpall, EJ, Nieto, Y, Ross, M, Peters, WP, and Jones, RB
- Published
- 1999
- Full Text
- View/download PDF
5. Successful allogeneic bone marrow transplantation in selected patients over 50 years of age – a single institution’s experience
- Author
-
Du, W, Dansey, R, Abella, EM, Baynes, R, Peters, WP, Klein, J, Akhtar, A, Cherednikova, L, and Karanes, C
- Published
- 1998
- Full Text
- View/download PDF
6. Reduced mortality following bone marrow transplantation for breast cancer with the addition of peripheral blood progenitor cells is due to a marked reduction in veno-occlusive disease of the liver
- Author
-
Fisher, DC, Vredenburgh, JJ, Petros, WP, Hussein, A, Berry, DA, Elkordy, M, Rubin, P, Gilbert, CJ, and Peters, WP
- Published
- 1998
- Full Text
- View/download PDF
7. A phase I trial of recombinant human interleukin-1β(OCT-43) following high-dose chemotherapy and autologous bone marrow transplantation
- Author
-
Elkordy, M, Crump, M, Vredenburgh, JJ, Petros, WP, Hussein, A, Rubin, P, Ross, M, Gilbert, C, Modlin, C, Meisenberg, B, Coniglio, D, Rabinowitz, J, Laughlin, M, Kurtzberg, J, and Peters, WP
- Published
- 1997
- Full Text
- View/download PDF
8. Taxanes with anthracyclines as first line chemotherapy for metastatic breast cancer: pooled analysis of 2805 patients
- Author
-
Bria, Emilio, Giannarelli, D, Felici, A, Peters, Wp, Nisticò, C, Vanni, B, Cuppone, F, Cognetti, F, and Terzoli, E.
- Subjects
anthracyclines ,Taxanes ,breast carcinoma - Published
- 2005
9. Amifostine (WR-2721) shortens the engraftment period of 4- hydroperoxycyclophosphamide-purged bone marrow in breast cancer patients receiving high-dose chemotherapy with autologous bone marrow support
- Author
-
Shpall, EJ, primary, Stemmer, SM, additional, Hami, L, additional, Franklin, WA, additional, Shaw, L, additional, Bonner, HS, additional, Bearman, SI, additional, Peters, WP, additional, Bast, RC Jr, additional, and McCulloch, W, additional
- Published
- 1994
- Full Text
- View/download PDF
10. Characterization of endogenous cytokine concentrations after high-dose chemotherapy with autologous bone marrow support
- Author
-
Rabinowitz, J, primary, Petros, WP, additional, Stuart, AR, additional, and Peters, WP, additional
- Published
- 1993
- Full Text
- View/download PDF
11. Comparative effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) on priming peripheral blood progenitor cells for use with autologous bone marrow after high-dose chemotherapy
- Author
-
Peters, WP, primary, Rosner, G, additional, Ross, M, additional, Vredenburgh, J, additional, Meisenberg, B, additional, Gilbert, C, additional, and Kurtzberg, J, additional
- Published
- 1993
- Full Text
- View/download PDF
12. Stimulation of ovarian tumor cell proliferation with monocyte products including interleukin-1, interleukin-6 and tumor necrosis factor-α
- Author
-
Wu, S, primary, Rodabaugh, K, additional, Martinez-Maza, O, additional, Watson, JM, additional, Silberstein, DS, additional, Boyer, CM, additional, Peters, WP, additional, Weinberg, JB, additional, Berek, JS, additional, and Bast, RC, additional
- Published
- 1992
- Full Text
- View/download PDF
13. Disposition of recombinant human granulocyte-macrophage colony- stimulating factor in patients receiving high-dose chemotherapy and autologous bone marrow support
- Author
-
Petros, WP, primary, Rabinowitz, J, additional, Stuart, AR, additional, Gilbert, CJ, additional, Kanakura, Y, additional, Griffin, JD, additional, and Peters, WP, additional
- Published
- 1992
- Full Text
- View/download PDF
14. High-dose alkylating agent chemotherapy with autologous bone marrow support in patients with stage III/IV epithelial ovarian cancer
- Author
-
Shpall, EJ, primary, Clarke-Pearson, D, additional, Soper, JT, additional, Berchuck, A, additional, Jones, RB, additional, Bast, RC, additional, Ross, M, additional, Lidor, Y, additional, Vanacek, K, additional, Tyler, T, additional, and Peters, WP, additional
- Published
- 1991
- Full Text
- View/download PDF
15. Neutrophil migration is defective during recombinant human granulocyte- macrophage colony-stimulating factor infusion after autologous bone marrow transplantation in humans
- Author
-
Peters, WP, Stuart, A, Affronti, ML, Kim, CS, and Coleman, RE
- Abstract
We have previously reported that continuous intravenous (IV) administration of recombinant granulocyte-macrophage colony-stimulating factor (rHuGM-CSF) to humans following high-dose alkylating agent chemotherapy and autologous bone marrow support (ABMS) results in myeloid bone marrow maturation, accelerated granulocyte recovery, and reduced treatment-related toxicity. However, we found that leukocyte counts declined rapidly after discontinuation of rHuGM-CSF therapy, which suggests possible growth factor effects on leukocyte margination and migration. For these reasons we studied granulocyte margination by using 111In-labeled autologous granulocytes and found similar granulocyte margination before (21.5% +/- 13.4%) and during continuous IV rHuGM-CSF infusion (23.3% +/- 9.6%). Phagocytosis of Cryptococcus neoformans and granulocyte hydrogen peroxide production was similar before and during rHuGM-CSF infusion and similar to patients treated with the same high-dose chemotherapy and ABMS but not receiving growth factor. However, migration of granulocytes to a sterile inflammatory site was markedly reduced during continuous rHuGM-CSF infusion (1.2 +/- 0.9 WBCs/cm2, 24 hr) as compared with baseline (39.6 +/- 17.7 WBCs/cm2/24 hr; P less than .0008). These findings may be of relevance when extravascular granulocytes are required for host defense.
- Published
- 1988
- Full Text
- View/download PDF
16. Detection of tumor cells in the bone marrow of stage IV breast cancer patients receiving high-dose chemotherapy: The role of induction chemotherapy
- Author
-
Vredenburgh, Jj, Peters, Wp, Rosner, G., Desombre, K., Johnston, Ww, Azza Kamel, Wu, K., and Bast, Rc
17. Cooperative groups are not...
- Author
-
Peters WP
- Published
- 2008
- Full Text
- View/download PDF
18. Impact of high-dose chemotherapy on the ability to deliver subsequent local-regional radiotherapy for breast cancer: analysis of Cancer and Leukemia Group B Protocol 9082.
- Author
-
Marks LB, Cirrincione C, Fitzgerald TJ, Laurie F, Glicksman AS, Vredenburgh J, Prosnitz LR, Shpall EJ, Crump M, Richardson PG, Schuster MW, Ma J, Peterson BL, Norton L, Seagren S, Henderson IC, Hurd DD, Peters WP, Cancer and Leukemia Group B, and Marks, Lawrence B
- Abstract
Purpose: To report, from Cancer and Leukemia Group B Protocol 9082, the impact of high-dose cyclophosphamide, cisplatin, and BCNU (HD-CPB) vs. intermediate-dose CPB (ID-CPB) on the ability to start and complete the planned course of local-regional radiotherapy (RT) for women with breast cancer involving >or=10 axillary nodes.Methods and Materials: From 1991 to 1998, 785 patients were randomized. The HD-CPB and ID-CPB arms were balanced regarding patient characteristics. The HD-CPB and ID-CPB arms were compared on the probability of RT initiation, interruption, modification, or incompleteness. The impact of clinical variables and interactions between variables were also assessed.Results: Radiotherapy was initiated in 82% (325 of 394) of HD-CPB vs. 92% (360 of 391) of ID-CPB patients (p = 0.001). On multivariate analyses, RT was less likely given to patients who were randomized to HD treatment (odds ratio [OR] = 0 .38, p < 0.001), older (p = 0.005), African American (p = 0.003), postmastectomy (p = 0.02), or estrogen receptor positive (p = 0.03). High-dose treatment had a higher rate of RT interruption (21% vs. 12%, p = 0.001, OR = 2.05), modification (29% vs. 14%, p = 0.001, OR = 2.46), and early termination of RT (9% vs. 2%, p = 0.0001, OR = 5.35), compared with ID.Conclusion: Treatment arm significantly related to initiation, interruption, modification, and early termination of RT. Patients randomized to HD-CPB were less likely to initiate RT, and of those who did, they were more likely to have RT interrupted, modified, and terminated earlier than those randomized to ID-CPB. The observed lower incidence of RT usage in African Americans vs. non-African Americans warrants further study. [ABSTRACT FROM AUTHOR]- Published
- 2010
- Full Text
- View/download PDF
19. Final results of a prematurely discontinued Phase 1/2 study of eniluracil with escalating doses of 5-fluorouracil administered orally in patients with advanced hepatocellular carcinoma.
- Author
-
de Lima Lopes G Jr, Dicksey JS, Peters WP, Palalay M, and Chang AY
- Subjects
- Administration, Oral, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Asian People, Carcinoma, Hepatocellular pathology, Dose-Response Relationship, Drug, Drug Resistance, Neoplasm, Female, Fluorouracil administration & dosage, Humans, Liver Neoplasms pathology, Male, Maximum Tolerated Dose, Middle Aged, Treatment Outcome, Uracil administration & dosage, Uracil analogs & derivatives, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy
- Abstract
Purpose: Eniluracil (EU) is a potent dihydropyrimidine (DPD) inhibitor, which improves the oral bio-availability of 5-fluorouracil (5-FU) and may overcome fluoropyrimidine (FP) resistance in hepatocellular carcinoma (HCC). Based on preclinical evidence, we aimed at studying a new dosing schedule for the combination with sequential administration, a lower dose of EU and higher doses of 5-FU than previously investigated., Methods: Patients with a diagnosis of hepatocellular carcinoma were eligible for this Phase 1/2 study. The primary endpoint for the Phase 1 was the determination of dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of oral 5-FU when given 14 h after oral EU 5 mg, weekly for 3 out of 4 weeks. The starting dose of 5-FU was 20 mg, followed by 30 mg and 80 mg. Secondary endpoints were anti-tumor activity, pharmacokinetics, and DPD activity in peripheral blood mononuclear cells. RECIST was used for assessment of efficacy and NCI CTC-AE version 3.0 for describing toxicity., Results: Nine patients enrolled in the trial. Median age was 53 years. All patients were Asian (one from Hawaii, 8 from Singapore). Prior treatment was as follows: liver surgery, 2 patients; chemo-embolization, 2 patients; thalidomide, 3 patients; adriamycin, 3 patients. Patients received a median of 2 cycles (range, 1-14) of therapy. No DLTs were seen up to the 80-mg 5-FU cohort. Out of 3 patients in the 80-mg cohort, one had pancytopenia. One patient at the 20-mg cohort had stable disease that lasted for 14 months., Conclusion: EU, at a 5.0-mg weekly dose, was well tolerated. There was no evidence of dose-related safety effects. This trial did not define the MTD for oral 5-FU. No objective responses by RECIST were noted but one patient had stable disease and a decrease of 28% in the sum of the largest diameters of her target lesions. The study was terminated early because of CNS-related toxicities noted in the single higher dose levels in a companion study, AHX-03-104.
- Published
- 2011
- Full Text
- View/download PDF
20. High-dose chemotherapy with autologous stem-cell support as adjuvant therapy in breast cancer: overview of 15 randomized trials.
- Author
-
Berry DA, Ueno NT, Johnson MM, Lei X, Caputo J, Rodenhuis S, Peters WP, Leonard RC, Barlow WE, Tallman MS, Bergh J, Nitz UA, Gianni AM, Basser RL, Zander AR, Coombes RC, Roché H, Tokuda Y, de Vries EG, Hortobagyi GN, Crown JP, Pedrazzoli P, Bregni M, and Demirer T
- Subjects
- Adult, Antineoplastic Agents adverse effects, Breast Neoplasms drug therapy, Breast Neoplasms mortality, Chemotherapy, Adjuvant, Combined Modality Therapy, Disease-Free Survival, Female, Humans, Middle Aged, Neoplasms, Second Primary, Randomized Controlled Trials as Topic, Transplantation, Autologous, Antineoplastic Agents administration & dosage, Breast Neoplasms therapy, Hematopoietic Stem Cell Transplantation
- Abstract
Purpose: Adjuvant high-dose chemotherapy (HDC) with autologous hematopoietic stem-cell transplantation (AHST) for high-risk primary breast cancer has not been shown to prolong survival. Individual trials have had limited power to show overall benefit or benefits within subsets., Methods: We assembled individual patient data from 15 randomized trials that compared HDC versus control therapy without stem-cell support. Prospectively defined primary end points were relapse-free survival (RFS) and overall survival (OS). We compared the effect of HDC versus control by using log-rank tests and proportional hazards regression, and we adjusted for clinically relevant covariates. Subset analyses were by age, number of positive lymph nodes, tumor size, histology, hormone receptor (HmR) status, and human epidermal growth factor receptor 2 (HER2) status., Results: Of 6,210 total patients (n = 3,118, HDC; n = 3,092 control), the median age was 46 years; 69% were premenopausal, 29% were postmenopausal, and 2% were unknown menopausal status; 49.5% were HmR positive; 33.5% were HmR negative, and 17% were unknown HmR status. The median follow-up was 6 years. After analysis was adjusted for covariates, HDC was found to prolong relapse-free survival (RFS; hazard ratio [HR], 0.87; 95% CI, 0.81 to 0.93; P < .001) but not overall survival (OS; HR, 0.94; 95% CI, 0.87 to 1.02; P = .13). For OS, no covariates had statistically significant interactions with treatment effect, and no subsets evinced a significant effect of HDC. Younger patients had a significantly better RFS on HDC than did older patients., Conclusion: Adjuvant HDC with AHST prolonged RFS in high-risk primary breast cancer compared with control, but this did not translate into a significant OS benefit. Whether HDC benefits patients in the context of targeted therapies is unknown.
- Published
- 2011
- Full Text
- View/download PDF
21. A phase 1 study of systemic ADH-1 in combination with melphalan via isolated limb infusion in patients with locally advanced in-transit malignant melanoma.
- Author
-
Beasley GM, McMahon N, Sanders G, Augustine CK, Selim MA, Peterson B, Norris R, Peters WP, Ross MI, and Tyler DS
- Subjects
- Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols pharmacokinetics, Chemotherapy, Cancer, Regional Perfusion, Drug Administration Schedule, Extremities, Female, Humans, Male, Melanoma pathology, Oligopeptides adverse effects, Oligopeptides agonists, Peptides, Cyclic adverse effects, Peptides, Cyclic agonists, Skin Neoplasms pathology, Survival Analysis, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Melanoma drug therapy, Melphalan administration & dosage, Oligopeptides administration & dosage, Peptides, Cyclic administration & dosage, Skin Neoplasms drug therapy
- Abstract
Background: Isolated limb infusion with melphalan is a well-tolerated treatment for patients with in-transit extremity melanoma with an approximately 30% complete response (CR) rate. ADH-1 is a cyclic pentapeptide that disrupts N-cadherin adhesion complexes and when given systemically in a preclinical model of regional melphalan therapy demonstrated synergistic antitumor activity. A phase 1 dose escalation study to evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of systemic ADH-1 in combination with melphalan via isolated limb infusion in patients with in-transit extremity melanoma was performed., Methods: Dose escalation cohorts of 3 patients each received 1000, 2000, and 4000 mg (10 patients) of ADH-1 administered intravenously on Days 1 and 8 with standard dose melphalan via isolated limb infusion on Day 1. N-cadherin immunohistochemistry staining and quantitative polymerase chain reaction analysis were performed on pretreatment tumor. Response was defined at 3 months using modified Response Evaluation Criteria in Solid Tumors., Results: Sixteen patients have been treated with no observed dose-limiting toxicities. Common treatment-related grade 1 or 2 toxicities included skin/dermatologic (n=14) and pain (n=12). Grade 3 toxicities included shortness of breath (n=1), hypertension (n=1), serologic toxicities (n=4), and 1 grade 4 creatine phosphokinase elevation. In-field responses included 8 CRs, 2 partial responses, 1 stable disease, and 5 progressive diseases. Pharmacokinetic analysis demonstrated increasing ADH-1 concentrations at each dose and minimal variability in melphalan drug levels., Conclusions: Systemic ADH-1 at a dose of 4000 mg on Days 1 and 8 in combination with melphalan via isolated limb infusion is a well-tolerated, novel targeted therapy approach to regionally advanced melanoma. The number of CRs exceeded expectations, suggesting that targeting N-cadherin may be a new strategy for overcoming melanoma chemoresistance., (Copyright (c) 2009 American Cancer Society.)
- Published
- 2009
- Full Text
- View/download PDF
22. Clinical and pharmacological phase I evaluation of Exherin (ADH-1), a selective anti-N-cadherin peptide in patients with N-cadherin-expressing solid tumours.
- Author
-
Perotti A, Sessa C, Mancuso A, Noberasco C, Cresta S, Locatelli A, Carcangiu ML, Passera K, Braghetti A, Scaramuzza D, Zanaboni F, Fasolo A, Capri G, Miani M, Peters WP, and Gianni L
- Subjects
- Antineoplastic Agents adverse effects, Antineoplastic Agents pharmacokinetics, Cadherins metabolism, Humans, Magnetic Resonance Imaging, Maximum Tolerated Dose, Neoplasms metabolism, Neoplasms pathology, Peptides, Cyclic adverse effects, Peptides, Cyclic pharmacokinetics, Antineoplastic Agents therapeutic use, Cadherins antagonists & inhibitors, Neoplasms drug therapy, Peptides, Cyclic therapeutic use
- Abstract
Background: Upregulation of N-cadherin promotes dysregulated cell growth, motility, invasiveness, plus maintenance of vascular stability and is associated with cancer progression in several human tumour types. N-cadherin is expressed also on tumour cells and the anti-N-cadherin cyclic pentapeptide ADH-1, tested in the present study, can exert a direct antitumour effect., Patients and Methods: Adult patients with advanced solid malignancies expressing N-cadherin on tumour biopsies carried out in the previous 12 months received escalating i.v. doses of ADH-1 given weekly (initially for 3 of 4 weeks, then every week). Plasma pharmacokinetics (PK) was studied at cycle 1. Blood flow changes were assessed after first dosing in all patients treated in the initial regimen., Results: In all, 129 patients were screened, 65 (50%) were N-cadherin positive, and 30 were enrolled. The doses ranged from 150 to 2400 mg/m(2); no maximum tolerated dose was reached. Treatment was well tolerated with asthenia as the most frequent adverse event. Two patients with ovarian cancer showed prolonged disease stabilisation while one patient with fallopian tube carcinoma achieved a mixed response. PK was linear in the range of doses tested., Conclusion: ADH-1 is the first anti-N-cadherin compound tested in humans. In N-cadherin-positive patients, ADH-1 showed an acceptable toxicity profile, linear PK and hints of antitumour activity in gynaecological cancers.
- Published
- 2009
- Full Text
- View/download PDF
23. Targeting N-cadherin enhances antitumor activity of cytotoxic therapies in melanoma treatment.
- Author
-
Augustine CK, Yoshimoto Y, Gupta M, Zipfel PA, Selim MA, Febbo P, Pendergast AM, Peters WP, and Tyler DS
- Subjects
- Animals, Cadherins chemistry, DNA Adducts chemistry, Dacarbazine analogs & derivatives, Dacarbazine pharmacology, Humans, Immunotherapy methods, Melanoma metabolism, Melphalan pharmacology, Models, Biological, Neoplasm Transplantation, Phenotype, Rats, Rats, Nude, Temozolomide, Antineoplastic Agents, Alkylating pharmacology, Cadherins metabolism, Melanoma drug therapy
- Abstract
Malignant transformation in melanoma is characterized by a phenotype "switch" from E- to N-cadherin, which is associated with increased motility and invasiveness of the tumor and altered signaling, leading to decreased apoptosis. We hypothesized that the novel pentapeptide (ADH-1), which disrupts N-cadherin adhesion, could sensitize melanoma tumors to the cytotoxic effects of chemotherapy. N-cadherin-expressing human melanoma-derived cell lines were used to generate xenografts in animal models to study isolated limb infusion with melphalan and systemic chemotherapy with temozolomide. We report here that melphalan in combination with ADH-1 significantly reduced tumor growth up to 30-fold over melphalan alone. ADH-1 enhancement of response to melphalan was associated with increased formation of DNA adducts, increased apoptosis, and intracellular signaling changes associated with focal adhesions and fibroblast growth factor receptors. Targeted therapy using an N-cadherin antagonist can dramatically augment the antitumor effects of chemotherapy and is a novel approach to optimizing treatment for melanoma.
- Published
- 2008
- Full Text
- View/download PDF
24. A randomized phase III comparative trial of immediate consolidation with high-dose chemotherapy and autologous peripheral blood progenitor cell support compared to observation with delayed consolidation in women with metastatic breast cancer and only bone metastases following intensive induction chemotherapy.
- Author
-
Vredenburgh JJ, Madan B, Coniglio D, Ross M, Broadwater G, Niedzwiecki D, Edwards J, Marks L, Vandemark R, McDonald C, Affronti ML, and Peters WP
- Subjects
- Adult, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Bone Neoplasms drug therapy, Bone Neoplasms radiotherapy, Bone Neoplasms therapy, Breast Neoplasms mortality, Combined Modality Therapy, Disease-Free Survival, Doxorubicin administration & dosage, Female, Fluorouracil administration & dosage, Humans, Methotrexate administration & dosage, Prognosis, Prospective Studies, Survival Rate, Time Factors, Transplantation, Autologous, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bone Neoplasms secondary, Breast Neoplasms drug therapy, Breast Neoplasms therapy, Peripheral Blood Stem Cell Transplantation
- Abstract
The prognosis for patients with metastatic breast cancer remains poor. Metastatic breast cancer confined to the bones may have a better prognosis, especially hormone receptor-positive disease. We performed a prospective, randomized clinical trial to compare immediate consolidation with high-dose chemotherapy and hematopoietic support versus observation with high-dose consolidation at the time of disease progression in women with metastatic breast cancer and only bone metastases. The patients received chemotherapy with doxorubicin, 5-fluorouracil and methotrexate before randomization. In all, 85 patients were enrolled and 69 were randomized. The median follow-up is 8.1 years from randomization. The median event-free survival (EFS) for the immediate transplant arm is 12 months and for the observation arm is 4.3 months (P<0.0001). The median overall survival for the immediate transplant arm is 2.97 years and for the observation arm 1.81 years, a difference that is not statistically significant. Immediate high-dose chemotherapy and radiation therapy as consolidation offers a clinically and statistically significant improvement in EFS compared with radiation therapy alone following induction chemotherapy for women with metastatic breast cancer confined to the bones.
- Published
- 2006
- Full Text
- View/download PDF
25. Consolidation with high-dose combination alkylating agents with bone marrow transplantation significantly improves disease-free survival in hormone-insensitive metastatic breast cancer in complete remission compared with intensive standard-dose chemotherapy alone.
- Author
-
Vredenburgh JJ, Coniglio D, Broadwater G, Jones RB, Ross M, Shpall EJ, Hussein A, Rizzieri D, Marks LB, Gilbert C, Affronti ML, Moore S, McDonald C, Petros WP, and Peters WP
- Subjects
- Adult, Alkylating Agents administration & dosage, Breast Neoplasms therapy, Disease-Free Survival, Female, Follow-Up Studies, Humans, Middle Aged, Recurrence, Remission Induction, S100 Calcium-Binding Protein A4, S100 Proteins, Salvage Therapy methods, Salvage Therapy mortality, Survival Rate, Transplantation, Homologous, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Bone Marrow Transplantation mortality, Breast Neoplasms mortality
- Abstract
We conducted this study to determine event-free and overall survival among women with hormone-insensitive or hormone-resistant metastatic breast cancer receiving consolidation with high-dose chemotherapy (HDC) and hematopoietic support versus no further chemotherapy after intensive induction chemotherapy. Eligible patients received induction doxorubicin, 5-fluorouracil, and methotrexate (AFM) for 2 to 4 cycles. Women in complete remission were randomized to immediate HDC with cyclophosphamide, cisplatin, and carmustine followed by autologous hematopoietic support or to no further therapy. Patients on the observation arm of therapy were offered salvage HDC at the time of relapse. Partial responders to AFM were offered immediate HDC. A total of 425 patients were enrolled onto the study. The median event-free survival for women randomized to induction therapy alone was 3.8 months, compared with 9.7 months for women who completed HDC (P < .006). Of the patients randomized to observation, 5 (10%) of 51 remain event free, compared with 13 (26%) of 49 patients who underwent immediate HDC (P = .03). Of women converted to a complete response by salvage HDC after a partial response to AFM, overall survival was similar to that in women randomized to immediate HDC. Follow-up is now in excess of 5 years. The 5-year event-free survival is 15% (95% confidence interval, 12%-18%), and the 5-year overall survival is 20% (95% confidence interval, 17%-25%). Immediate HDC after a complete response to AFM produced some durable long-term responses in hormone-insensitive/-resistant metastatic breast cancer. Salvage HDC converted 30% of partial responders to complete responders with similar survivals. The addition of novel targeted therapies to intensive-dose chemotherapy regimens may further improve survival in metastatic breast cancer.
- Published
- 2006
- Full Text
- View/download PDF
26. Associations between drug metabolism genotype, chemotherapy pharmacokinetics, and overall survival in patients with breast cancer.
- Author
-
Petros WP, Hopkins PJ, Spruill S, Broadwater G, Vredenburgh JJ, Colvin OM, Peters WP, Jones RB, Hall J, and Marks JR
- Subjects
- Adult, Breast Neoplasms pathology, Carmustine administration & dosage, Carmustine pharmacokinetics, Cisplatin administration & dosage, Cisplatin pharmacokinetics, Cyclophosphamide administration & dosage, Cyclophosphamide pharmacokinetics, Female, Genotype, Humans, Middle Aged, Prognosis, Survival Analysis, Antineoplastic Combined Chemotherapy Protocols pharmacokinetics, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms drug therapy, Breast Neoplasms genetics, Polymorphism, Genetic
- Abstract
Purpose: To evaluate associations between patient survival, pharmacokinetics, and drug metabolism-related genetic polymorphisms in patients receiving a combination chemotherapy regimen for breast cancer., Patients and Methods: A genotype association study was conducted on 85 chemotherapy-naïve patients with metastatic or inflammatory breast cancer that were evaluated for an extended period after receiving standard-dose chemotherapy followed by high-dose cyclophosphamide, cisplatin, and carmustine. Blood pharmacokinetics were evaluated, and DNA was genotyped for 29 polymorphisms in 17 drug metabolism genes., Results: Patients with cyclophosphamide plasma exposures above the median (implying slower metabolic activation) had a shorter survival than those below the median (1.8 v 3.8 years, respectively; P = .042). Patients having a variant genotype of cytochrome P450 3A4 displayed higher blood concentrations of parent (inactive) cyclophosphamide with the second and third doses (P = .024 and .028, respectively) in addition to slower cyclophosphamide activation over the three doses (P = .031). Median survival for these patients was 1.3 years compared with 2.7 years for those without the variant (P = .043). Similar results were observed for patients carrying a genetic variant of P450 3A5. Median survival for patients with deletions of glutathione-S-transferase M1 gene was 3.5 v 1.5 years for patients with one or both copies (P = .041). Patients with a polymorphism in a gene regulating metallothionein had lower platinum concentrations and shorter survival (P = .033)., Conclusion: These data suggest that pretreatment evaluation of drug metabolism genes may explain some interindividual differences in both anticancer drug pharmacokinetics and response. The correlations found here may have implications for other commonly used anticancer drugs.
- Published
- 2005
- Full Text
- View/download PDF
27. Prospective, randomized comparison of high-dose chemotherapy with stem-cell support versus intermediate-dose chemotherapy after surgery and adjuvant chemotherapy in women with high-risk primary breast cancer: a report of CALGB 9082, SWOG 9114, and NCIC MA-13.
- Author
-
Peters WP, Rosner GL, Vredenburgh JJ, Shpall EJ, Crump M, Richardson PG, Schuster MW, Marks LB, Cirrincione C, Norton L, Henderson IC, Schilsky RL, and Hurd DD
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Breast Neoplasms surgery, Carmustine administration & dosage, Chemotherapy, Adjuvant, Cisplatin administration & dosage, Cyclophosphamide administration & dosage, Disease-Free Survival, Dose-Response Relationship, Drug, Female, Granulocyte Colony-Stimulating Factor administration & dosage, Humans, Middle Aged, Neoplasm Staging, Peripheral Blood Stem Cell Transplantation, Prognosis, Prospective Studies, Risk Factors, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms drug therapy, Breast Neoplasms genetics, Lymphatic Metastasis
- Abstract
Purpose: The prognosis for women with primary breast cancer involving multiple axillary nodes remains poor. High-dose chemotherapy with stem-cell support produced promising results in initial clinical trials conducted at single institutions., Patients and Methods: Seven hundred eighty-five women aged 22 to 66 years with stage IIA, IIB, or IIIA breast cancer involving 10 or more axillary lymph nodes were randomized after surgery and standard adjuvant chemotherapy to either high-dose cyclophosphamide, cisplatin, and carmustine (HD-CPB) with stem-cell support or intermediate-dose cyclophosphamide, cisplatin, and carmustine (ID-CPB) with G-CSF support but without stem cells. Planned treatment for all patients included locoregional radiation therapy. Hormone-receptor-positive patients were to receive 5 years of tamoxifen. Event-free survival (EFS) was the primary end point., Results: Median follow-up was 7.3 years. Event-free survival was not significantly different between the two treatment groups (P = .24). The probability of being free of an event at 5 years with HD-CPB was 61% (95% CI, 56% to 65%), and was 58% (95% CI, 53% to 63%) for ID-CPB. Thirty-three patients died of causes attributed to HD-CPB, compared with no therapy-related deaths among women treated with ID-CPB. Overall survival for the two arms was identical at 71% at 5 years (P = .75)., Conclusion: HD-CPB with stem-cell support was not superior to ID-CPB for event-free or overall survival among all randomized women with high-risk primary breast cancer.
- Published
- 2005
- Full Text
- View/download PDF
28. Taxanes with anthracyclines as first-line chemotherapy for metastatic breast carcinoma.
- Author
-
Bria E, Giannarelli D, Felici A, Peters WP, Nisticò C, Vanni B, Cuppone F, Cognetti F, and Terzoli E
- Subjects
- Anthracyclines adverse effects, Antineoplastic Agents adverse effects, Breast Neoplasms mortality, Clinical Trials as Topic, Humans, Survival Analysis, Taxoids adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Breast Neoplasms drug therapy
- Abstract
Background: The magnitude of the benefit of adding taxanes to anthracyclines in first-line chemotherapy for metastatic breast carcinoma is still unclear. The authors performed a pooled analysis as well as a meta-analysis of all Phase III trials, to determine whether the combination of anthracyclines plus taxanes provided an advantage over standard anthracyclines-based regimens., Methods: All Phase III peer-reviewed published or presented trials were considered eligible. A pooled analysis (Method A) and a literature-based meta-analysis (Method B) were accomplished, and event-based relative risk ratios (RR(A-B)) with 95% confidence intervals were derived. Both analyses were performed to examine for significant differences in time to disease progression (TTP), overall response rate (ORR), overall survival (OS), complete response rate (CR), neutropenia, and febrile neutropenia (FN). For both analyses, a heterogeneity test was applied., Results: Seven trials (2805 patients) were gathered. When data were pooled and plotted, significant differences in favor of taxanes were seen for ORR (RR(A-B) 1.21, P<0.001), CR (RR(A) 2.04; RR(B) 1.81, P<0.001), even though they caused a significant increase in neutropenia (RR(A) 1.19; RR(B) 1.15, P<0.001) and FN (RR(A) 2.82; RR(B) 3.44, P<0.001). A borderline significance in favor of taxanes was seen in TTP (RR(A) 1.10, P=0.05; RR(B) 1.06, P=0.07). A nonsignificant trend for taxanes was found in OS. No significant heterogeneity (except for neutropenia, P<0.01) was observed., Conclusions: The adjunction of taxanes to anthracyclines in first-line chemotherapy for metastatic breast carcinoma yielded a significant benefit in activity (ORR, CR), a slight advantage in TTP, and a trend in OS, although with a significant cost in hematologic toxicity., (Copyright (c) 2005 American Cancer Society.)
- Published
- 2005
- Full Text
- View/download PDF
29. The analysis of relapse-free survival curves: implications for evaluating intensive systemic adjuvant treatment regimens for breast cancer.
- Author
-
Day RS, Shackney SE, and Peters WP
- Subjects
- Axilla, Combined Modality Therapy, Female, Humans, Lymphatic Metastasis, Time Factors, Tumor Burden, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Breast Neoplasms drug therapy, Chemotherapy, Adjuvant, Disease-Free Survival, Models, Biological, Neoplasm Recurrence, Local prevention & control
- Abstract
Results of adjuvant dose intensification studies in patients with localised breast cancer have raised questions regarding the clinical usefulness of this treatment strategy. Here, we develop and fit a natural history model for the time to clinical tumour recurrence as a function of the number of involved lymph nodes, and derive plausible predictions of the effects of dose intensification under various conditions. The time to tumour recurrence is assumed to depend on the residual postoperative micrometastatic burden of tumour, the fractional reduction of residual tumour burden (RTB) by treatment, and the rate of regrowth of the RTB to a clinically detectable size. It is assumed that a proportion of micrometastatic tumours are unresponsive to adjuvant chemotherapy even at maximal dose intensity. Data fitted included the San Antonio Cancer Institute (SACI) database of untreated patients, and CALGB #9082, a study comparing a highly intensive and moderately intensity adjuvant regimen in patients with 10+ positive axillary nodes. The proportion of tumours unresponsive to maximally intensive adjuvant treatment is estimated to be 48% (29-67%). The estimated log kill for intermediate-dose therapy from CALGB #9082 was 6.5 logs, compared with 9 logs or greater for high-dose therapy. The model is consistent with a modest but nonnegligible advantage of dose intensification compared with standard therapies in patients with sensitive tumours who have 10+ positive axillary nodes, and suggests that much of this clinical benefit could be achieved using intermediate levels of treatment intensification. The model further suggests that, in patients with fewer than 10 involved axillary nodes, any advantage of treatment intensification over standard therapy would be much reduced, because in patients with smaller tumour burdens of sensitive tumour, a larger proportion of cures achievable with intensified therapy could be achieved as well with standard therapy.
- Published
- 2005
- Full Text
- View/download PDF
30. Cost-effectiveness and lung cancer clinical trials.
- Author
-
Du W, Reeves JH, Gadgeel S, Abrams J, and Peters WP
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols economics, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Non-Small-Cell Lung diagnosis, Carcinoma, Non-Small-Cell Lung therapy, Confidence Intervals, Cost-Benefit Analysis, Female, Hospital Costs, Humans, Lung Neoplasms diagnosis, Lung Neoplasms therapy, Male, Middle Aged, Neoplasm Staging, Patient Selection, Pneumonectomy economics, Probability, Proportional Hazards Models, Radiotherapy, Adjuvant economics, Carcinoma, Non-Small-Cell Lung economics, Clinical Trials as Topic economics, Health Care Costs, Insurance, Health economics, Lung Neoplasms economics
- Abstract
Background: Lung cancer is the leading cause of cancer death in the U.S., with an estimated annual economic burden of $5 billion. Clinical trials offer innovative therapeutic options with potentially better outcomes, but their effects on health care costs are disputed., Methods: The authors analyzed the 1-year facility-based treatment cost and survival of 336 newly diagnosed nonsmall cell lung cancer patients who were deemed eligible for clinical trials between 1994 and 1998 at the Karmanos Cancer Institute. The incremental cost-effectiveness ratio (ICER) of clinical trial treatments with adjustment for confounders was calculated along with its 95% confidence interval (CI) using the bootstrap resampling method., Results: Of the 336 patients, 76 (22.6%) were treated on clinical trials. Trial participation was associated significantly with race (P < 0.01), gender (P = 0.01), age (P = 0.02), and insurance type (P = 0.02). The average 1-year cost for trial enrollees was $41,734 with a median survival of 1.3 years, whereas the average 1-year cost for nonenrollees was $34,191 with a median survival period of 0.9 years. Differences in survival and 1-year cost between enrollees and nonenrollees were significant when controlling for age, race, gender, insurance, stage, performance status, and comorbidities. The ICER for trial participation after adjustment for confounders was $9741 per life year saved (95% CI, $3089-$19,149)., Conclusions: Enrollment in lung cancer clinical trials was found to be associated with improved survival at a moderate incremental cost. Cancer 2003;98:1491-6., (Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11659)
- Published
- 2003
- Full Text
- View/download PDF
31. Association of high-dose cyclophosphamide, cisplatin, and carmustine pharmacokinetics with survival, toxicity, and dosing weight in patients with primary breast cancer.
- Author
-
Petros WP, Broadwater G, Berry D, Jones RB, Vredenburgh JJ, Gilbert CJ, Gibbs JP, Colvin OM, and Peters WP
- Subjects
- Adult, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols pharmacokinetics, Area Under Curve, Breast Neoplasms metabolism, Breast Neoplasms secondary, Carmustine administration & dosage, Carmustine adverse effects, Carmustine pharmacokinetics, Cisplatin administration & dosage, Cisplatin adverse effects, Cisplatin pharmacokinetics, Cyclophosphamide administration & dosage, Cyclophosphamide adverse effects, Cyclophosphamide pharmacokinetics, Disease-Free Survival, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Humans, Lymphatic Metastasis, Survival Rate, Time Factors, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Body Weight drug effects, Breast Neoplasms drug therapy
- Abstract
This report investigates relationships between the pharmacokinetics and pharmacodynamics of high-dose alkylators used for the treatment of primary breast cancer. Eighty-five women with primary breast cancer involving >or=10 lymph nodes received four cycles of standard-dose chemotherapy followed by a high-dose regimen consisting of: cyclophosphamide (1875 mg/m(2) once daily x 3), cisplatin (165 mg/m(2) given over 72 h), carmustine (600 mg/m(2)), and stem cell transplantation. Dosages were attenuated in patients whose body weight exceeded their calculated ideal weight by >20%. Pharmacokinetics of the high-dose chemotherapeutic agents were evaluated in each patient by collection and analysis of serial blood samples. Area under the concentration time curve (AUC) for cyclophosphamide and carmustine was highly variable (>10-fold inter-patient range) with coefficients of variation > 50%, in contrast to cisplatin exposures (2-fold range; coefficient of variation 12%). The dosing method for overweight patients resulted in significantly lower systemic exposure to cisplatin (P = 0.035). The parent cyclophosphamide clearance on the 1st day of administration was significantly higher in patients who experienced acute cardiac toxicity (n = 5; P = 0.011), whereas carmustine disposition was not found to be different in those developing pulmonary toxicity (n = 25; P = 0.96). Kaplan-Meier analysis (median follow-up of 5.9 years) demonstrated that patients with lower cyclophosphamide AUC (faster parent drug clearance to potentially cytotoxic compounds) survived longer (P = 0.031). Inter-individual differences in the pharmacokinetic disposition of high-dose chemotherapy may explain variability in both response and toxicity. Prospective strategies, which attempt to individualize AUC, should be evaluated in this setting.
- Published
- 2002
32. High-dose chemotherapy and hematopoietic support for patients with high-risk primary breast cancer and involvement of 4 to 9 lymph nodes.
- Author
-
Stuart MJ, Peters WP, Broadwater G, Hussein A, Ross M, Marks LB, Folz RJ, Long GD, Rizzieri D, Chao NJ, and Vredenburgh JJ
- Subjects
- Adult, Antineoplastic Combined Chemotherapy Protocols adverse effects, Breast Neoplasms drug therapy, Breast Neoplasms mortality, Breast Neoplasms surgery, Carmustine administration & dosage, Cisplatin administration & dosage, Combined Modality Therapy, Cyclophosphamide administration & dosage, Female, Granulocyte Colony-Stimulating Factor therapeutic use, Humans, Middle Aged, Multivariate Analysis, Patient Selection, Recombinant Proteins, Regression Analysis, Survival Analysis, Transplantation, Autologous, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms pathology, Breast Neoplasms therapy, Lymphatic Metastasis, Stem Cell Transplantation
- Abstract
Despite modern chemotherapy, advanced breast cancer remains a significant cause of cancer morbidity and mortality in women. Patients with disease involvement of multiple lymph nodes represent a subgroup with a high risk of relapse. In particular, 50% of patients with 4 to 9 axillary lymph nodes involved will relapse after standard chemotherapy. In an effort to improve the survival of patients with 4 to 9 involved nodes, we performed a phase II study in which 61 patients with surgically diagnosed stage II or III breast cancer and 4 to 9 positive lymph nodes received 3 cycles of doxorubicin and 5-fluorouracil followed by high-dose chemotherapy consisting of cisplatin, cyclophosphamide, and carmustine and infusion of autologous hematopoietic progenitor cells. All patients received posttransplantation localized radiotherapy unless contraindicated, and all patients with hormone receptor-positive disease received tamoxifen. After a median patient follow-up of 6.7 years (range, 4.6-8.6 years), the 5-year overall survival rate was 79% (95% CI, 69%-90%), with relapse-free survival of 73% (95% CI, 62%-85%). Treatment-related mortality was 3%. Interstitial pneumonitis occurred in 69% of patients but did not contribute to mortality. Our study presents long-term favorable results regarding the use of consolidative HDC with autologous hematopoietic support in previously untreated patients with high-risk primary breast cancer.
- Published
- 2002
- Full Text
- View/download PDF
33. High-dose chemotherapy and hematopoietic stem cell transplantation for breast cancer: past or future?
- Author
-
Baynes RD, Dansey RD, Klein JL, Hamm C, Campbell M, Abella E, and Peters WP
- Subjects
- Clinical Trials as Topic, Female, Humans, Antineoplastic Agents therapeutic use, Breast Neoplasms therapy, Hematopoietic Stem Cell Transplantation
- Abstract
Given that each year in the United States 180,000 new cases of breast cancer are diagnosed, with about 44,000 women succumbing to the disease, and that breast cancer is the second leading cause of cancer-related death in women, it is clear that existing therapy fails a large number of patients. Recently, a number of novel strategies have been developed in attempts to improve survival. These include agents used at very high dose requiring stem cell support. High-dose chemotherapy (HDC) with hematopoietic stem cell transplantation (HSCT), most frequently in the form of peripheral blood progenitor cell transplantation (PBPCT), is an highly active treatment approach in appropriate patients and the current data relating to this modality will be reviewed here. This article will attempt to place the recent randomized studies in perspective, to highlight the strengths and limitations of the data, and to offer some thoughts on future directions for the field.
- Published
- 2001
- Full Text
- View/download PDF
34. Cost analysis of pancreatic carcinoma treatment.
- Author
-
Du W, Touchette D, Vaitkevicius VK, Peters WP, and Shields AF
- Subjects
- Aged, Combined Modality Therapy, Costs and Cost Analysis, Female, Health Care Costs, Humans, Insurance, Health, Male, Middle Aged, Multivariate Analysis, Pancreatic Neoplasms mortality, Pancreatic Neoplasms therapy, Survival Analysis, United States, Pancreatic Neoplasms economics
- Abstract
Background: Pancreatic carcinoma is a major health issue and financial burden to society. To improve the quality and efficiency of care delivered, it is essential for health care providers to have a good understanding of the cost of treatment., Methods: The authors examined the facility-based costs and survival of 103 patients with pancreatic carcinoma who were treated at the Karmanos Cancer Institute between January 1992 and September 1998. Longitudinal cost data for each patient were obtained, and from those data, 6-month, 1-year, and lifetime total treatment costs were calculated., Results: The average 6-month, 1-year, and lifetime total treatment costs were $37,327, $42,218, and $48,803, respectively, and the median survival was 7 months. In univariate analyses, the disease stage at diagnosis was a highly significant predictor of total cost. Patients with metastatic disease had the lowest cost, and patients with resectable disease had the highest cost. In multivariate analyses controlling for disease stage, treatment strategies and dual insurance coverage were also important predictors of costs but patient age, race, and gender were not predictive. Disease stage also was highly predictive of survival. In a multivariate analysis controlling for disease stage, chemotherapy and radiation therapy were correlated with longer survival, whereas resection and palliative bypass surgery were not., Conclusions: The costs of treating patients with pancreatic carcinoma are considerable, even though survival duration typically is short. Disease stage was the most dominating factor determining costs and survival. After controlling for disease stage, chemotherapy, surgery, and dual insurance coverage were also significantly associated with higher cost of care. However, in survival analyses, only chemotherapy and radiation therapy were associated with a significant increase in patient survival., (Copyright 2000 American Cancer Society.)
- Published
- 2000
- Full Text
- View/download PDF
35. Bone marrow and peripheral blood hematopoietic stem cell transplantation: focus on autografting.
- Author
-
Baynes RD, Hamm C, Dansey R, Klein J, Cassells L, Karanes C, Abella E, and Peters WP
- Subjects
- Breast Neoplasms drug therapy, Breast Neoplasms radiotherapy, Breast Neoplasms therapy, Combined Modality Therapy, Female, Hodgkin Disease drug therapy, Hodgkin Disease radiotherapy, Hodgkin Disease therapy, Humans, Leukemia, Myeloid drug therapy, Leukemia, Myeloid radiotherapy, Leukemia, Myeloid therapy, Lymphoma, Non-Hodgkin drug therapy, Lymphoma, Non-Hodgkin radiotherapy, Lymphoma, Non-Hodgkin therapy, Multiple Myeloma drug therapy, Multiple Myeloma radiotherapy, Multiple Myeloma therapy, Neoplasms drug therapy, Neoplasms radiotherapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma radiotherapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Randomized Controlled Trials as Topic, Transplantation, Autologous, Bone Marrow Transplantation, Hematopoietic Stem Cell Transplantation, Neoplasms therapy
- Abstract
This review focuses on certain of the principles involved in high-dose chemotherapy and radiation therapy along with autologous hematopoietic stem cell transplantation for the treatment of certain malignancies. In addition, the evidence, wherever possible based on randomized data, for the application of this approach in certain malignancies is reviewed. The malignancies highlighted include acute myeloid leukemia, acute lymphoblastic leukemia, non-Hodgkin lymphoma, Hodgkin disease, and breast cancer.
- Published
- 2000
36. High-dose chemotherapy and peripheral blood progenitor cell transplantation in the treatment of breast cancer.
- Author
-
Peters WP, Dansey RD, Klein JL, and Baynes RD
- Subjects
- Breast Neoplasms drug therapy, Clinical Trials as Topic, Combined Modality Therapy, Dose-Response Relationship, Drug, Female, Humans, Prognosis, Research Design, Risk Factors, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms therapy, Hematopoietic Stem Cell Transplantation
- Abstract
Each year in the USA, 180,000 new cases of breast cancer are diagnosed and about 44,000 women die of the disease. Current primary treatment consists of adjuvant chemotherapy and hormone therapy, and statistics show that combination chemotherapy favorably influences the outcomes in both node-negative and node-positive primary disease. However, a significant number of breast cancer patients succumb to the disease, and nearly every patient diagnosed with metastatic breast cancer will be dead within five years. High-dose chemotherapy (HDC) and peripheral blood progenitor cell transplantation (PBPCT) are based upon laboratory and clinical observations of the ability to modify growth properties of quiescent and replicating cancer cells. A large number of HDC and PBPCT regimens have been evaluated for treatment of metastatic breast cancer, and recent autologous bone marrow transplantation data indicate that three HDC regimens (CPB, CTCb and cytoxan and thiotepa) predominate. Unfortunately, negative media coverage surrounding and subsequent to the presentation of preliminary findings reported at the May 1999 American Society of Clinical Oncologists, that were not allowed adequate follow-up time for full analysis of treatment results, has had a detrimental effect on the ability to conduct trials in this area. Several randomized trials have been conducted in both the metastatic and high risk primary disease settings. Thorough analysis of these studies indicates an evaluable improvement in favor of HDC and PBPCT in three of the four randomized studies performed in metastatic breast cancer and two of the four high risk primary studies. Also, initial evaluations found that quality of life appeared comparable in patients receiving either HDC or not. Each randomized trial studied asks a different question and, depending on the intensity of HDC regimen, the intensity and duration of the standard dose chemotherapy control and the schedule of events in relation to induction chemotherapy, the outcomes may be quite variable. Still, certain general trends are indentifiable. HDC alone will not completely cure breast cancer and should be considered as part of an overall therapeutic plan. In some of these studies, significantly longer follow-up is required before definitive analysis can be completed.
- Published
- 2000
- Full Text
- View/download PDF
37. High-dose chemotherapy and autologous stem cell transplantation for breast cancer.
- Author
-
Baynes RD, Dansey RD, Klein JL, Karanes C, Cassells L, Abella E, Wei WZ, Galy A, Du W, Wood G, and Peters WP
- Subjects
- Agranulocytosis chemically induced, Agranulocytosis therapy, Antineoplastic Combined Chemotherapy Protocols adverse effects, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Chemotherapy, Adjuvant, Dose-Response Relationship, Drug, Female, Humans, Neoplasm Metastasis, Quality of Life, Time Factors, Transplantation, Autologous, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms therapy, Hematopoietic Stem Cell Transplantation
- Published
- 2000
- Full Text
- View/download PDF
38. Prognostic and predictive factors for patients with metastatic breast cancer undergoing aggressive induction therapy followed by high-dose chemotherapy with autologous stem-cell support.
- Author
-
Rizzieri DA, Vredenburgh JJ, Jones R, Ross M, Shpall EJ, Hussein A, Broadwater G, Berry D, Petros WP, Gilbert C, Affronti ML, Coniglio D, Rubin P, Elkordy M, Long GD, Chao NJ, and Peters WP
- Subjects
- Adult, Breast Neoplasms pathology, Combined Modality Therapy, Doxorubicin administration & dosage, Estrogen Antagonists administration & dosage, Female, Fluorouracil administration & dosage, Humans, Methotrexate administration & dosage, Middle Aged, Predictive Value of Tests, Prognosis, Retrospective Studies, Survival Analysis, Tamoxifen administration & dosage, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms drug therapy, Hematopoietic Stem Cell Transplantation
- Abstract
Purpose: We performed a retrospective review to determine predictive and prognostic factors in patients with metastatic breast cancer who received induction therapy, and, if they responded to treatment, high-dose chemotherapy., Patients and Methods: Patients with metastatic breast cancer received induction therapy with doxorubicin, fluorouracil, and methotrexate (AFM). Partial responders then received immediate high-dose chemotherapy, whereas those who achieved complete remission were randomized to immediate or delayed high-dose chemotherapy with hematopoietic stem-cell support. We performed a retrospective review of data from these patients and used Cox proportional hazards regression models for analyses., Results: The overall response rate for the 425 patients enrolled was 74% (95% confidence interval, 70% to 78%). Multivariate analysis of data from all 425 patients revealed that positive estrogen receptor status (P =.0041), smaller metastatic foci (= 2 v > 2 cm) (P =. 0165), a longer disease-free interval from initial diagnosis to diagnosis of metastases (= 2 v > 2 years) (P =.0051), and prior treatment with tamoxifen (P =.0152) were good prognostic signs for overall survival. Patients who had received prior adjuvant therapy (P =.0001) and those who developed liver metastases (P =.0001) had decreased long-term survival. In the subgroup of responders to AFM induction, multivariate analysis showed that those with visceral metastases did less well (P =.0006), as did patients who had received prior adjuvant therapy (P =.0023). However, those who had received tamoxifen therapy in the adjuvant setting did better (P =. 0143)., Conclusion: The chance for long-term remission with induction therapy with AFM and high-dose chemotherapy is increased for hormone receptor positive-patients with nonvisceral metastases who have not received prior adjuvant chemotherapy and have long disease-free intervals.
- Published
- 1999
- Full Text
- View/download PDF
39. Impact of consolidation radiotherapy in patients with advanced breast cancer treated with high-dose chemotherapy and autologous bone marrow rescue.
- Author
-
Carter DL, Marks LB, Bean JM, Broadwater G, Hussein A, Vredenburgh JJ, Peters WP, and Prosnitz LR
- Subjects
- Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bone Marrow Transplantation, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Combined Modality Therapy, Humans, Middle Aged, Remission Induction, Transplantation, Autologous, Breast Neoplasms radiotherapy
- Abstract
Purpose: To examine the impact of consolidation radiotherapy (RT) after high-dose chemotherapy with autologous bone marrow rescue (HDC) in patients with advanced breast cancer., Patients and Methods: Between 1988 and 1994,425 patients with metastatic or recurrent breast cancer received doxorubicin, fluorouracil, and methotrexate (AFM) induction chemotherapy in a single-institution prospective trial. One hundred patients who achieved a complete response were randomized to receive HDC (cyclophosphamide, cisplatin, carmustine), with autologous bone marrow rescue immediately after AFM, or to observation, with HDC to be administered at next relapse. Seventy-four of the 100 became eligible for RT; 53 received consolidation RT (HDC RT+ and 21 did not (HDC RT-). The assignment of RT was not randomized. The RT+ and RT- groups were similar with regard to number of involved sites, the fraction of patients with only local-regional disease, age, and interval since initial diagnosis. Local control at previously involved sites and distant sites was assessed with extensive radiologic and clinical evaluations at the time of first failure or most recent follow-up. The impact of RT on failure patterns, event-free survival, and overall survival was evaluated., Results: Sites of first failure were located exclusively at previously involved sites in 28% of RT+ patients versus 62% of RT- patients (P < .01). Event-free survival at 4 years was 31% and 21% in the RT+ and RT-groups, respectively (P = .02). Overall survival at 4 years was 30% and 16% in the RT+ and RT- groups, respectively (P = .20)., Conclusion: Patients with advanced breast cancer who were treated with HDC without RT failed predominantly at the initial sites of disease. The addition of RT appeared to reduce the failure rate at initial disease sites and may improve event-free and overall survival. Our observations await verification in a trial in which assignment to RT is randomized.
- Published
- 1999
- Full Text
- View/download PDF
40. The addition of paclitaxel to continuous infusion 5-fluorouracil is an active regimen for metastatic breast cancer.
- Author
-
Vredenburgh J, Fishman R, Coniglio D, Matters L, Elkordy M, Ross M, Hussein A, Rubin P, Gilbert C, Petros W, and Peters WP
- Subjects
- Adult, Breast Neoplasms pathology, Female, Fluorouracil administration & dosage, Humans, Middle Aged, Neoplasm Metastasis, Paclitaxel administration & dosage, Remission Induction, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms drug therapy
- Abstract
Metastatic breast cancer is commonly thought to be incurable. Treatment advances have resulted in increased response rates, although such responses are often more palliative than curative. A regimen of continuous infusion 5-fluorouracil (5FU) or continuous infusion 5-fluorouracil with paclitaxel was studied in patients with metastatic breast cancer and measurable disease. The induction therapy preceded high-dose ifosfamide, carboplatin, and melphalan in a phase I-II trial. Eighty-seven patients were enrolled in the trial. Forty-five received continuous infusion 5-fluorouracil as induction and 42 received 5-fluorouracil and paclitaxel. The single-agent, continuous infusion 5-fluorouracil cohort had one complete response (2%) and eight partial responses (18%). The combination continuous infusion 5-fluorouracil and 3-hour paclitaxel regimen produced four complete responses (10%) and 17 partial responses (40%). The combination regimen of continuous infusion 5-fluorouracil with bolus paclitaxel was well tolerated and with a 50% response rate, is an active regimen for women with metastatic breast cancer.
- Published
- 1998
- Full Text
- View/download PDF
41. Effect of plasma TNF-alpha on filgrastim-stimulated hematopoiesis in mice and humans.
- Author
-
Petros WP, Rabinowitz J, Gibbs JP, Hall IH, Stuart AR, and Peters WP
- Subjects
- Adult, Animals, Blood Platelets cytology, Blood Platelets drug effects, Blood Platelets metabolism, Breast Neoplasms blood, Breast Neoplasms drug therapy, Dose-Response Relationship, Drug, Erythrocytes cytology, Erythrocytes drug effects, Erythrocytes metabolism, Female, Filgrastim, Glycoproteins administration & dosage, Glycoproteins therapeutic use, Granulocyte Colony-Stimulating Factor administration & dosage, Granulocyte-Macrophage Colony-Stimulating Factor administration & dosage, Granulocyte-Macrophage Colony-Stimulating Factor therapeutic use, Humans, Immunologic Factors administration & dosage, Immunologic Factors therapeutic use, Leukocytes cytology, Leukocytes drug effects, Leukocytes metabolism, Lipopolysaccharides pharmacology, Male, Melanoma blood, Melanoma drug therapy, Mice, Middle Aged, Multivariate Analysis, Recombinant Proteins, Treatment Outcome, Tumor Necrosis Factor-alpha metabolism, Granulocyte Colony-Stimulating Factor therapeutic use, Hematopoiesis drug effects, Tumor Necrosis Factor-alpha drug effects
- Abstract
Study Objective: To delineate possible explanations for a nonmonotone hematopoiesis, dose-response curve with filgrastim therapy after high-dose chemotherapy, Design: Sequential two-phase study., Settings: University teaching hospital and basic pharmaceutical sciences laboratory., Subjects: Thirty-nine patients with breast cancer or melanoma and 15 normal CF-1 male mice., Interventions: Serial blood samples were obtained from patients after high-dose chemotherapy to evaluate hematopoiesis and tumor necrosis factor-alpha (TNF-alpha) concentrations. Murine hematopoiesis was induced by filgrastim with or without coadministration of lipopolysaccharide., Measurements and Main Results: Detection of plasma TNF-alpha in patients corresponded to substantially slower recovery of granulocytes, erythrocytes, and platelets, and was directly proportional to the prescribed dosage of filgrastim. Lipopolysaccharide stimulated the secretion of TNF-alpha in mice and totally aberrated filgrastim-induced granulopoiesis., Conclusions: This in vivo evidence suggests that regulatory pathways involving endogenous cytokines may override the effect of recombinant cytokines.
- Published
- 1998
42. Secondary myelodysplasia and acute leukemia in breast cancer patients after autologous bone marrow transplant.
- Author
-
Laughlin MJ, McGaughey DS, Crews JR, Chao NJ, Rizzieri D, Ross M, Gockerman J, Cirrincione C, Berry D, Mills L, Defusco P, LeGrand S, Peters WP, and Vredenburgh JJ
- Subjects
- Acute Disease, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carmustine administration & dosage, Chromosome Aberrations, Cisplatin administration & dosage, Combined Modality Therapy, Cyclophosphamide administration & dosage, Female, Humans, Karyotyping, Leukemia genetics, Myelodysplastic Syndromes genetics, Retrospective Studies, Survival Analysis, Transplantation, Autologous, Antineoplastic Combined Chemotherapy Protocols adverse effects, Bone Marrow Transplantation adverse effects, Breast Neoplasms therapy, Leukemia etiology, Myelodysplastic Syndromes etiology
- Abstract
Purpose: To determine the incidence of myelodysplasia (MDS) and/or acute leukemia (AL) in breast cancer patients after high-dose chemotherapy (HDC) with a single conditioning regimen and autologous bone marrow transplant (ABMT), and analyze the cytogenetic abnormalities that arise after HDC., Patients and Methods: We retrospectively reviewed the records of 864 breast cancer patients who underwent ABMT at Duke University Medical Center, Durham, NC, from 1985 through 1996 who received the same preparative regimen of cyclophosphamide 1,875 mg/m2 for 3 days, cisplatin 55 mg/m2 for 3 days, and BCNU 600 mg/m2 for 1 day (CPB). Pretransplant cytogenetics were analyzed in all patients and posttransplant cytogenetics were evaluated in four of five patients who developed MDS/AL., Results: Five of 864 patients developed MDS/AL after HDC with CPB and ABMT. The crude cumulative incidence of MDS/AL was 0.58%. The Kaplan-Meier curve shows a 4-year probability of developing MDS/AL of 1.6%. Pretransplant cytogenetics performed on these five patients were all normal. Posttransplant cytogenetics were performed on four of five patients and they were abnormal in all four, although only one patient had the most common cytogenetic abnormality associated with secondary MDS/AL (chromosome 5 and/or 7 abnormality)., Conclusion: Whereas MDS/AL is a potential complication of HDC with CPB and ABMT, the incidence in this series of patients with breast cancer was relatively low compared with that reported in patients with non-Hodgkin's lymphoma who underwent ABMT. The cytogenetic abnormalities reported in this group of breast cancer patients were not typical of those seen in prior reports of secondary MDS/AL and appear to have occurred after HDC.
- Published
- 1998
- Full Text
- View/download PDF
43. Pharmacokinetic interaction between ondansetron and cyclophosphamide during high-dose chemotherapy for breast cancer.
- Author
-
Gilbert CJ, Petros WP, Vredenburgh J, Hussein A, Ross M, Rubin P, Fehdrau R, Cavanaugh C, Berry D, McKinstry C, and Peters WP
- Subjects
- Antiemetics therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms therapy, Carmustine administration & dosage, Cisplatin administration & dosage, Combined Modality Therapy, Cyclophosphamide administration & dosage, Dose-Response Relationship, Drug, Doxorubicin administration & dosage, Drug Interactions, Fluorouracil administration & dosage, Hematopoietic Stem Cell Transplantation, Humans, Methotrexate administration & dosage, Ondansetron therapeutic use, Prospective Studies, Transplantation Conditioning, Antiemetics pharmacokinetics, Antineoplastic Combined Chemotherapy Protocols pharmacokinetics, Breast Neoplasms drug therapy, Cyclophosphamide pharmacokinetics, Ondansetron pharmacokinetics
- Abstract
Purpose: Both ondansetron and cyclophosphamide are thought to be metabolized by hepatic microsomal processes. The purpose of this study was to evaluate the potential pharmacokinetic interactions between ondansetron and high-dose alkylating agent chemotherapy., Methods: A total of 54 breast cancer patients receiving high-dose cyclophosphamide, cisplatin and carmustine were treated prospectively in four sequential cohorts. Cohorts I and II received continuous infusions of both ondansetron and prochlorperazine, and cohorts III and IV received a continuous infusion of ondansetron alone at the same doses. All patients received lorazepam every 4 h. A group of 75 matched historical controls had received a continuous infusion of prochlorperazine with lorazepam. Pharmacokinetic monitoring of each drug used in the high-dose chemotherapy regimen was conducted., Results: Median AUCs of cyclophosphamide in patients receiving ondansetron (73.6 mg/ml x min) were lower than those of the control patients (88.3 mg/ml x min, n = 75, P = 0.0004), but the median cisplatin AUC was approximately 10% higher and no difference in the disposition of carmustine was demonstrated. Patients treated with ondansetron displayed a higher frequency of headaches than the controls. The frequency of achieving complete emetic control was greater in the ondansetron + prochlorperazine groups compared to the ondansetron alone groups and was greater in both these groups than in the prochlorperazine alone group on the first day of therapy only., Conclusion: Ondansetron altered the systemic exposure to cyclophosphamide when these agents were administered concomitantly. Ondansetron did not substantially improve overall emetic control when used alone but may improve control in combination with prochlorperazine. Future randomized studies are needed to delineate the effect of ondansetron on the disposition of the active cyclophosphamide metabolites so that clinical implications can be addressed.
- Published
- 1998
- Full Text
- View/download PDF
44. A randomized trial of recombinant human interleukin-11 following autologous bone marrow transplantation with peripheral blood progenitor cell support in patients with breast cancer.
- Author
-
Vredenburgh JJ, Hussein A, Fisher D, Hoffman M, Elkordy M, Rubin P, Gilbert C, Kaye JA, Dykstra K, Loewy J, and Peters WP
- Subjects
- Adult, Aged, Combined Modality Therapy, Female, Humans, Middle Aged, Transplantation, Autologous, Bone Marrow Transplantation, Breast Neoplasms therapy, Hematopoietic Stem Cell Transplantation, Interleukin-11 administration & dosage, Recombinant Proteins administration & dosage
- Abstract
This study assessed the safety and efficacy of recombinant human interleukin (rhIL)-11 in decreasing platelet transfusion requirements in patients with breast cancer who were undergoing autologous bone marrow transplantation (ABMT) with peripheral blood progenitor cell (PBPC) support. After high-dose therapy with cyclophosphamide, cisplatin, and carmustine, 80 patients were randomized to one of three treatment groups: placebo (26), 25 microg/kg of rhIL-11 (28), and 50 microg/kg of rhIL-11 (26). Of those randomized, 75 (94%) received at least one dose of the masked study drug and the remaining 5 (6%) withdrew consent before study drug administration. In the placebo group, each patient received an average 12.4 (+/-10.2) platelet transfusions vs. 9.2 (+/-5.0) in the 25-microg/kg rhIL-11 group (p = 0.17) and 9.9 (+/-3.5) in the 50-microg/kg rhIL-11 group (p = 0.34). There was no statistically significant difference between the rhIL-11 groups and the placebo group in the median number of days to platelet recovery. Neutrophil and red blood cell recovery were similar for all treatment groups. The imbalance in the number of patients already alloimmunized at study entry in the rhIL-11 groups (12) and in the placebo group (1) may have confounded the primary efficacy assessment. Most adverse events were related to the high-dose chemotherapy. Generally mild edema and minor conjunctival bleeding (grades 1 or 2) were statistically associated with rhIL-11 administration (p < 0.04). There was no association between rhIL-11 and the occurrence of atrial arrhythmias, although there was a suggestion of an association with rhIL-11, 5 of 50 cases vs. 1 of 25 in the placebo group. Two cardiovascular events, tachycardia and hypotension (grade 1 or 2), occurred in the 50-microg/kg rhIL-11 group. The number of patients who discontinued study drug dosing because of an adverse event was distributed across all treatment groups. In summary, rhIL-11 was safe and well tolerated in this study. The results did not demonstrate that rhIL-11 treatment significantly decreased platelet transfusion requirements after high-dose chemotherapy with ABMT and PBPC support.
- Published
- 1998
- Full Text
- View/download PDF
45. The significance of tumor contamination in the bone marrow from high-risk primary breast cancer patients treated with high-dose chemotherapy and hematopoietic support.
- Author
-
Vredenburgh JJ, Silva O, Broadwater G, Berry D, DeSombre K, Tyer C, Petros WP, Peters WP, and Bast RC Jr
- Subjects
- Adult, Breast Neoplasms mortality, Breast Neoplasms pathology, Disease-Free Survival, Dose-Response Relationship, Drug, Female, Humans, Lymphatic Metastasis, Middle Aged, Pilot Projects, Prognosis, Risk Factors, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bone Marrow pathology, Breast Neoplasms drug therapy, Hematopoietic Stem Cell Transplantation
- Abstract
We studied the incidence and significance of tumor cell contamination of the bone marrow or peripheral blood progenitor cells of patients who had high risk primary breast cancer involving 10 or more axillary lymph nodes and who received high dose cyclophosphamide, cisplatin, and carmustine with hematopoietic support as consolidation following standard dose adjuvant chemotherapy. The autologous hematopoietic cell products were evaluated in 85 eligible patients. Eighty-three samples were available from the time of bone marrow harvest, and peripheral blood progenitor cells were evaluated from 57 of the 65 patients who additionally received these products. The screening technique utilized a panel of four anti-breast cancer monoclonal antibodies and an immunohistochemical technique. Thirty (36%) of the 83 evaluable patients had tumor cell contamination of the bone marrow. Only 2 (4%) of the 57 patients had tumor cell contamination of the peripheral blood progenitor cells. Tumor cell contamination of the bone marrow was associated with shorter disease-free survival and overall survival. In addition, the higher the number of tumor cells identified, the shorter disease-free and overall survival. There was no relationship between the tumor cell contamination of the bone marrow and the site of relapse. The combination of the log of the number of tumor cells +1 and number of positive lymph nodes predicted both disease-free and overall survival. Tumor cell contamination of the bone marrow from the harvest is associated with shorter disease-free and overall survival for patients who were treated with standard dose chemotherapy followed by consolidation with high dose alkylating agents and hematopoietic support. It is unclear what role the contaminating tumor cells have in relapse, and they may just be a high-risk marker. A comparison with other prognostic factors and characteristics of the tumor may determine the significance of the tumor contamination of the bone marrow.
- Published
- 1997
46. Clinical pharmacology of filgrastim following high-dose chemotherapy and autologous bone marrow transplantation.
- Author
-
Petros WP, Rabinowitz J, Stuart A, and Peters WP
- Subjects
- Adult, Antineoplastic Combined Chemotherapy Protocols adverse effects, Carmustine administration & dosage, Cisplatin administration & dosage, Combined Modality Therapy, Cyclophosphamide administration & dosage, Female, Filgrastim, Granulocyte Colony-Stimulating Factor adverse effects, Granulocyte Colony-Stimulating Factor pharmacokinetics, Humans, Leukocyte Count drug effects, Metabolic Clearance Rate, Recombinant Proteins, Regression Analysis, Transplantation, Autologous, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bone Marrow Transplantation adverse effects, Breast Neoplasms therapy, Granulocyte Colony-Stimulating Factor therapeutic use, Melanoma therapy
- Abstract
We evaluated the pharmacokinetics and pharmacodynamics of filgrastim during a Phase I study of this cytokine following high-dose chemotherapy and autologous bone marrow transplantation. Serum granulocyte colony-stimulating factor concentrations were determined by ELISA in 21 patients receiving 14-day continuous i.v. filgrastim infusions and 10 patients receiving daily 4-h infusions. Models were developed for filgrastim systemic clearance (Cls) by incorporation of receptor-binding theory. Mean plasma half-life (t1/2) in the 4-h infusion group was 197 min, and the volume of distribution approximated plasma volume. WBC counts transiently fell, then rebounded immediately postinfusion, which correlated with a delay in the disappearance of serum granulocyte colony-stimulating factor. The effect of WBC concentrations on filgrastim Cls was determined in patients receiving continuous infusions by segregation of study periods based on the presence of severe neutropenia. Clearance increased in all 14 patients receiving doses of 4-32 microgram/kg/day during WBC recovery. The effect of WBCs on Cls was described by a differential equation that included a static component and one component that varied with WBC concentration. These data suggest that currently used filgrastim dosing strategies following autologous bone marrow transplantation may be suboptimal.
- Published
- 1997
47. Relation of glutathione S-transferase alpha and mu isoforms to response to therapy in human breast cancer.
- Author
-
Alpert LC, Schecter RL, Berry DA, Melnychuk D, Peters WP, Caruso JA, Townsend AJ, and Batist G
- Subjects
- Adult, Breast Diseases enzymology, Breast Diseases pathology, Breast Neoplasms mortality, Breast Neoplasms pathology, Female, Follow-Up Studies, Humans, Immunohistochemistry methods, Lymphatic Metastasis, Menopause, Middle Aged, Receptors, Estrogen analysis, Receptors, Progesterone analysis, Survival Analysis, Time Factors, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bone Marrow Transplantation, Breast enzymology, Breast Neoplasms enzymology, Breast Neoplasms therapy, Glutathione Transferase analysis, Hematopoietic Stem Cell Transplantation, Isoenzymes analysis
- Abstract
Glutathione S-transferase (GST) represents a multifunctional enzyme family consisting of four known cytosolic isoforms (alpha, mu, pi, and Phi) that detoxify a variety of xenobiotic chemicals and may confer resistance to both chemotherapeutic drugs and carcinogens in various experimental models. GST-pi has already been extensively studied in clinical specimens, including breast cancer. We studied the immuno-histochemical distribution and relative immunopositivity of GST-alpha and GST-mu, based on a grading system for immunointensity, in samples of 51 neoplastic and 46 normal breast samples and 12 lymph node metastases from patients treated with intensive chemotherapy and bone marrow transplant. In normal breast tissue, GST-alpha localized predominantly to the cytoplasm of scattered cells lining the luminal aspects of the ducts. Occasional cells showed both cytoplasmic and nuclear GST-alpha immunoreactivity. GST-mu was stained in myoepithelial cells preferentially as well as in occasional ductal cells (including apocrine epithelium), vascular smooth muscle, and plasma cells. GST-alpha and GST-mu were detected in 22 of 51 (43%) and 24 of 48 (50%) invasive cancers, respectively. In paired samples of normal and malignant tissue from the same patient, GST-alpha immunostaining in cancers was significantly less intense compared to that of normal breast tissue in 13 of 41 (32%) cases. No such trend was found for GST-mu in paired samples. Neither GST-alpha nor GST-mu immunopositivity in tumor or nonneoplastic breast was found to correlate with relapse-free or overall survival in this clinical context; however, the apparent decreased expression of GST-alpha in malignant versus normal breast epithelial cells could have important implications in breast carcinogenesis.
- Published
- 1997
48. New concepts in the treatment of breast cancer using high-dose chemotherapy.
- Author
-
Peters WP and Dansey R
- Subjects
- Breast Neoplasms pathology, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Humans, Randomized Controlled Trials as Topic, Survival Analysis, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Breast Neoplasms drug therapy
- Abstract
High-dose chemotherapy is now frequently used for the treatment of primary and metastatic breast cancer. Two recent randomized trials have demonstrated that this treatment approach can result in extended disease-free and overall survival for patients with metastatic disease. However, treatment results have demonstrated that long term remissions from these treatments raise complex questions about traditional models of chemotherapy principles. A detailed analysis of the principles underlying high-dose therapy is presented in the context of principles of dose-response, the inverse rule and the total tumor cell kill hypotheses.
- Published
- 1997
- Full Text
- View/download PDF
49. The pharmacologic effects of recombinant, human colony-stimulating factors and their modulation by theophylline.
- Author
-
Petros WP, Rosner GL, Rabinowitz J, Gilbert CJ, Coniglio D, Vredenburgh JJ, Ross M, and Peters WP
- Subjects
- Adult, Aminophylline administration & dosage, Area Under Curve, Breast Neoplasms blood, Breast Neoplasms therapy, Combined Modality Therapy, Female, Granulocyte Colony-Stimulating Factor administration & dosage, Granulocyte-Macrophage Colony-Stimulating Factor administration & dosage, Half-Life, Hematopoietic Stem Cell Transplantation, Humans, Metabolic Clearance Rate, Middle Aged, Prospective Studies, Recombinant Proteins, Aminophylline pharmacokinetics, Aminophylline pharmacology, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cytokines blood, Granulocyte Colony-Stimulating Factor pharmacology, Granulocyte-Macrophage Colony-Stimulating Factor pharmacology
- Abstract
Study Objectives: To investigate the effect of colony-stimulating factors (CSFs) on drug metabolism using theophylline as a substrate (phase I), and to evaluate the influence of theophylline on endogenous serum cytokine concentrations (phase II)., Design: Open-label, prospective study., Setting: The bone marrow transplant unit of a tertiary university teaching hospital., Patients: Thirty-seven women with breast cancer (28 phase I, 9 phase II)., Interventions: Patients received aminophylline 0.58 mg/kg either as a 30-minute intravenous infusion before receiving recombinant CSFs or after several days of CSF therapy, just before high-dose chemotherapy (phase I) or as a continuous intravenous infusion after bone marrow transplantation (phase II)., Measurements and Main Results: Clearance of theophylline was significantly higher after CSF administration (0.76 vs 0.99 ml/min/kg, p = 0.019). Continuous infusion of aminophylline resulted in elevations of serum macrophage-CSF and interleukin 6., Conclusions: Administration of CSFs before autologous bone marrow transplantation for priming progenitor cells may alter drug metabolism. Studies should be conducted to evaluate the potential effects of CSFs on the disposition of chemotherapeutic agents.
- Published
- 1996
50. Evaluation of symptom distress in a bone marrow transplant outpatient environment.
- Author
-
Lawrence CC, Gilbert CJ, and Peters WP
- Subjects
- Adult, Ambulatory Care, Antineoplastic Combined Chemotherapy Protocols adverse effects, Bone Marrow Transplantation psychology, Breast Neoplasms psychology, Cisplatin adverse effects, Combined Modality Therapy, Cyclophosphamide adverse effects, Female, Humans, Middle Aged, Nausea chemically induced, Nausea prevention & control, Patient Compliance, Prospective Studies, Surveys and Questionnaires, Transplantation, Autologous, Vomiting chemically induced, Vomiting prevention & control, Bone Marrow Transplantation adverse effects, Breast Neoplasms therapy
- Abstract
Objective: To measure patient perceptions of autologous bone marrow transplantation (ABMT)-associated symptoms in the outpatient setting, assess the efficacy of the established antiemetic protocol, evaluate patient satisfaction, and report patient medication compliance., Design: A prospective, descriptive study of patients with breast cancer who were enrolled in an outpatient ABMT program., Setting: Duke University Autologous Bone Marrow Transplantation Program., Methods: Patient perceptions of 12 symptoms were measured by the Symptom Distress Scale (SDS) on the day of admission to the hospital, the day of discharge to the outpatient clinic, after bone marrow reinfusion, and before patient release from the clinic. The number of retching and vomiting episodes was recorded by each patient daily. Patient satisfaction was determined by a standardized personal interview conducted prior to discharge. Patient compliance was assessed by a review of patient medication documentation., Results: Twenty-eight patients were enrolled over 5 months. The median SDS scores for each symptom evaluated revealed that anorexia, nausea, fatigue, insomnia, and bowel problems were the most distressing symptoms patients experienced in the outpatient ABMT program. Scores for pain, negative outlook, cough, diminished concentration, and change in appearance indicated only mild distress associated with these variables. The total number of vomiting episodes ranged from 1 to 33 total episodes per patient per outpatient stay. The percentage of patients experiencing a complete antiemetic response ranged from 24% to 48% over the 4 days after chemotherapy but steadily improved thereafter to a peak of 90% 1 week later. Patient satisfaction results showed that patients preferred being out of the hospital and reported their anxiety controlled although most had some problems with the outpatient clinic or medications required., Conclusions: Loss of appetite, fatigue, and insomnia have been identified as symptoms that are frequently present during the course of the outpatient ABMT program. Mild, intermittent nausea persists in the outpatient setting for up to 9 days after bone marrow transplant despite continuous combination antiemetic therapy. Patient interviews confirmed the belief that patients enjoy being out of the hospital. Medication compliance is more than 90% in this structured outpatient setting.
- Published
- 1996
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.