31 results on '"Cooper MR"'
Search Results
2. Phase III study of cyclophosphamide, doxorubicin, and fluorouracil (CAF) plus leucovorin versus CAF for metastatic breast cancer: Cancer and Leukemia Group B 9140.
- Author
-
Parnes HL, Cirrincione C, Aisner J, Berry DA, Allen SL, Abrams J, Chuang E, Cooper MR, Perry MC, Duggan DB, Szatrowski TP, Henderson IC, and Norton L
- Subjects
- Aged, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Breast Neoplasms pathology, Cyclophosphamide administration & dosage, Disease Progression, Doxorubicin administration & dosage, Female, Fluorouracil administration & dosage, Health Status, Humans, Leucovorin administration & dosage, Middle Aged, Neoplasm Metastasis, Prognosis, Survival, Treatment Outcome, Viscera pathology, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms drug therapy
- Abstract
Purpose: To determine whether biochemical modulation with LV (leucovorin) enhances the efficacy of CAF (cyclophosphamide, doxorubicin, and fluorouracil) against metastatic breast cancer., Patients and Methods: Women with histologically confirmed stage IV breast cancer, Cancer and Leukemia Group B (CALGB) performance status 0 to 2, and no prior chemotherapy for metastatic disease were randomly assigned to receive CAF (cyclophosphamide 500 mg/m2 day 1, doxorubicin 40 mg/m2 day 1, and fluorouracil [FU] 200 mg/m2 intravenous bolus days 1 to 5) with or without LV (LV 200 mg/m2 over 30 minutes days 1 to 5 given 1 hour before FU)., Results: Two hundred forty-two patients were randomly assigned to treatment; 124 patients had visceral crisis and 40 patients had a CALGB performance status score of 2. The median follow-up was 6 years. The two study arms were similar with regard to serious adverse events; four patients died from treatment-related causes, two patients on each study arm. Predictive variables for time to treatment failure and survival were visceral disease and performance status. The overall response rate was 29% for CAF versus 28% for CAF plus LV. The median time to treatment failure (9 months) and median survival (1.7 years) did not differ by treatment arm., Conclusion: Modulation of CAF with LV improved neither response rates nor survival among women with metastatic breast cancer, compared with CAF alone. Multivariate analyses confirmed the prognostic importance of performance status and visceral crisis. However, the overall and complete response rates, response durations, time to treatment failure, and survival were the same in the two treatment arms.
- Published
- 2003
- Full Text
- View/download PDF
3. Improved outcomes from adding sequential Paclitaxel but not from escalating Doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer.
- Author
-
Henderson IC, Berry DA, Demetri GD, Cirrincione CT, Goldstein LJ, Martino S, Ingle JN, Cooper MR, Hayes DF, Tkaczuk KH, Fleming G, Holland JF, Duggan DB, Carpenter JT, Frei E 3rd, Schilsky RL, Wood WC, Muss HB, and Norton L
- Subjects
- Adult, Aged, Antibiotics, Antineoplastic administration & dosage, Disease-Free Survival, Dose-Response Relationship, Drug, Doxorubicin administration & dosage, Female, Humans, Lymphatic Metastasis, Middle Aged, Proportional Hazards Models, Treatment Outcome, Antineoplastic Agents, Phytogenic administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Paclitaxel administration & dosage
- Abstract
Purpose: This study was designed to determine whether increasing the dose of doxorubicin in or adding paclitaxel to a standard adjuvant chemotherapy regimen for breast cancer patients would prolong time to recurrence and survival., Patients and Methods: After surgical treatment, 3,121 women with operable breast cancer and involved lymph nodes were randomly assigned to receive a combination of cyclophosphamide (C), 600 mg/m(2), with one of three doses of doxorubicin (A), 60, 75, or 90 mg/m(2), for four cycles followed by either no further therapy or four cycles of paclitaxel at 175 mg/m(2). Tamoxifen was given to 94% of patients with hormone receptor-positive tumors., Results: There was no evidence of a doxorubicin dose effect. At 5 years, disease-free survival was 69%, 66%, and 67% for patients randomly assigned to 60, 75, and 90 mg/m(2), respectively. The hazard reductions from adding paclitaxel to CA were 17% for recurrence (adjusted Wald chi(2) P =.0023; unadjusted Wilcoxon P =.0011) and 18% for death (adjusted P =.0064; unadjusted P =.0098). At 5 years, the disease-free survival (+/- SE) was 65% (+/- 1) and 70% (+/- 1), and overall survival was 77% (+/- 1) and 80% (+/- 1) after CA alone or CA plus paclitaxel, respectively. The effects of adding paclitaxel were not significantly different in subsets defined by the protocol, but in an unplanned subset analysis, the hazard ratio of CA plus paclitaxel versus CA alone was 0.72 (95% confidence interval, 0.59 to 0.86) for those with estrogen receptor-negative tumors and only 0.91 (95% confidence interval, 0.78 to 1.07) for patients with estrogen receptor-positive tumors, almost all of whom received adjuvant tamoxifen. The additional toxicity from adding four cycles of paclitaxel was generally modest., Conclusion: The addition of four cycles of paclitaxel after the completion of a standard course of CA improves the disease-free and overall survival of patients with early breast cancer.
- Published
- 2003
- Full Text
- View/download PDF
4. Alemtuzumab in previously treated chronic lymphocytic leukemia patients who also had received fludarabine.
- Author
-
Rai KR, Freter CE, Mercier RJ, Cooper MR, Mitchell BS, Stadtmauer EA, Santábarbara P, Wacker B, and Brettman L
- Subjects
- Adolescent, Alemtuzumab, Antibodies, Monoclonal, Humanized, Antigens, CD metabolism, Antimetabolites, Antineoplastic therapeutic use, Antineoplastic Agents adverse effects, DNA (Cytosine-5-)-Methyltransferases antagonists & inhibitors, Female, Humans, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Leukemia, Prolymphocytic, T-Cell pathology, Male, Neutropenia chemically induced, Opportunistic Infections, Pilot Projects, Remission Induction, Salvage Therapy, Survival Rate, Thrombocytopenia chemically induced, Treatment Failure, Treatment Outcome, Vidarabine adverse effects, Vidarabine analogs & derivatives, Antibodies, Monoclonal therapeutic use, Antibodies, Neoplasm therapeutic use, Antineoplastic Agents therapeutic use, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Leukemia, Prolymphocytic, T-Cell drug therapy, Vidarabine therapeutic use
- Abstract
Purpose: This phase II pilot study determined the efficacy and safety of alemtuzumab (Campath-1H; Burroughs Wellcome, United Kingdom) in patients with chronic lymphocytic leukemia (CLL), all of whom had previously received fludarabine and other chemotherapy regimens., Patients and Methods: Twenty-four patients were treated with intravenous alemtuzumab at six centers in the United States. The target dose of 30 mg over 2 hours, three times weekly, was administered for up to 16 weeks. Responses were evaluated by an independent panel of experts using 1996 National Cancer Institute-sponsored Working Group criteria. Safety assessments included analysis of lymphocyte subpopulations. Antimicrobial prophylaxis was not mandatory., Results: Eight patients (33%) achieved a major response (all partial remissions), with a median time to response of 3.9 months (range, 1.6 to 5.3 months). The median duration of response was 15.4 months (range, 4.6 to >or= 38.0 months), the median time to disease progression was 19.6 months (range, 7.7 to >or= 42.0 months), and the median survival time was 35.8 months (range, 8.8 to >or= 47.1 months). Acute infusion-related events, mainly grades 1 and 2, were most common and most severe in the first week. Ten patients (eight nonresponders and two responders) experienced major infections on-study. Pneumocystis carinii pneumonia was reported in two patients on-study; neither had received prophylaxis. Median CD4+ and CD8+ counts decreased and then began to increase by the end of the study, with further recovery by 1-month follow-up. One of 53 samples obtained from 10 patients had a low titer of alemtuzumab antibodies., Conclusion: Alemtuzumab has significant activity in poor-prognosis, fludarabine-treated CLL patients. However, because of a relatively high incidence of opportunistic infections accompanying profound lymphopenia, future protocols should include mandatory prophylaxis.
- Published
- 2002
- Full Text
- View/download PDF
5. Phase I study of anti--epidermal growth factor receptor antibody cetuximab in combination with radiation therapy in patients with advanced head and neck cancer.
- Author
-
Robert F, Ezekiel MP, Spencer SA, Meredith RF, Bonner JA, Khazaeli MB, Saleh MN, Carey D, LoBuglio AF, Wheeler RH, Cooper MR, and Waksal HW
- Subjects
- Adult, Aged, Antibodies, Monoclonal therapeutic use, Antibodies, Monoclonal, Humanized, Antineoplastic Agents therapeutic use, Cetuximab, Combined Modality Therapy, Dose-Response Relationship, Drug, Female, Humans, Male, Metabolic Clearance Rate, Middle Aged, Antibodies, Monoclonal pharmacology, Antineoplastic Agents pharmacology, Carcinoma, Squamous Cell therapy, Head and Neck Neoplasms therapy, Radiotherapy methods
- Abstract
Purpose: To evaluate the safety, pharmacokinetics, and efficacy of a chimeric anti-epidermal growth factor receptor monoclonal antibody, cetuximab, in combination with radiation therapy (RT) in patients with advanced squamous cell carcinoma of the head and neck., Patients and Methods: We treated 16 patients in five successive treatment schedules. A standard dose escalation procedure was used; three patients entered onto the study at each dose level of cetuximab received conventional RT (70 Gy, 2 Gy/d), and the final three patients received hyperfractionated RT (76.8 Gy, 1.2 Gy bid). Cetuximab was delivered as a loading dose of 100 to 500 mg/m(2), followed by weekly infusions of 100 to 250 mg/m(2) for 7 to 8 weeks. Circulating levels of cetuximab during therapy were determined using a biomolecular interaction analysis core instrument. Human antichimeric antibody response was evaluated with a double-antigen radiometric assay. The recommended phase II/III dose was defined as the optimal cetuximab dose level based on the pharmacologic parameters and adverse events., Results: The most commonly reported adverse events were fever, asthenia, transaminase elevation, nausea, and skin toxicities (grade 1 to 2 in most patients). Skin toxicity outside of the RT field was not strictly dose-dependent; however, grade 2 or higher events were observed in patients treated with higher dose regimens. There was one grade 4 allergic reaction. Most acute adverse effects were associated with RT (xerostomia, mucositis, and local skin toxicity). No antibodies against cetuximab were detected. All patients achieved an objective response (13 complete and two partial remissions)., Conclusion: Cetuximab can be safely administered with RT. The recommended dose for phase II/III studies is a loading dose of 400 to 500 mg/m(2) and a maintenance weekly dose of 250 mg/m(2).
- Published
- 2001
- Full Text
- View/download PDF
6. Phase I studies of anti-epidermal growth factor receptor chimeric antibody C225 alone and in combination with cisplatin.
- Author
-
Baselga J, Pfister D, Cooper MR, Cohen R, Burtness B, Bos M, D'Andrea G, Seidman A, Norton L, Gunnett K, Falcey J, Anderson V, Waksal H, and Mendelsohn J
- Subjects
- Adult, Antibodies, Monoclonal adverse effects, Antibodies, Monoclonal pharmacokinetics, Antibodies, Monoclonal, Humanized, Antineoplastic Agents adverse effects, Antineoplastic Agents pharmacokinetics, Area Under Curve, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung therapy, Carcinoma, Squamous Cell drug therapy, Carcinoma, Squamous Cell therapy, Cetuximab, Dose-Response Relationship, Drug, Drug Administration Schedule, ErbB Receptors genetics, Female, Gene Expression Regulation, Neoplastic, Head and Neck Neoplasms drug therapy, Head and Neck Neoplasms therapy, Humans, Infusions, Intravenous, Lung Neoplasms drug therapy, Lung Neoplasms therapy, Male, Neoplasms, Glandular and Epithelial drug therapy, Recombinant Fusion Proteins adverse effects, Recombinant Fusion Proteins pharmacokinetics, Remission Induction, Safety, Antibodies, Monoclonal therapeutic use, Antineoplastic Agents therapeutic use, Cisplatin therapeutic use, ErbB Receptors antagonists & inhibitors, Neoplasms, Glandular and Epithelial therapy, Recombinant Fusion Proteins therapeutic use
- Abstract
Purpose: The epidermal growth factor (EGF) receptor is frequently overexpressed in epithelial tumors. C225 is a human-to-murine chimeric monoclonal antibody that binds to the receptor and inhibits growth of cancer cells expressing the receptor. We evaluated the pharmacokinetics and toxicity of C225 in patients with advanced tumors overexpressing EGF receptors., Patients and Methods: We treated 52 patients in three successive phase I clinical trials of C225 as a single dose (n = 13), weekly multiple dose (n = 17), and weekly multiple dose with cisplatin (n = 22). C225 dose levels were 5, 20, 50, and 100 mg/m(2). In the study combining C225 with cisplatin, limited to patients with either head and neck or non-small-cell lung cancer, C225 was further escalated to 200 and 400 mg/m(2). Cisplatin was given at a dose of 60 mg/m(2) once every 4 weeks, and treatment was continued for up to 12 weeks if no disease progression occurred., Results: C225 displayed nonlinear pharmacokinetics, with antibody doses in the range of 200 to 400 mg/m(2) being associated with complete saturation of systemic clearance. C225 clearance did not change with repeated administration or with coadministration of cisplatin. Antibodies against C225 were detected in only one patient, and C225-associated toxicity was minimal. Patients experiencing disease stabilization were seen in all studies. In the study combining C225 and cisplatin, nine (69%) of 13 patients treated with antibody doses >/= 50 mg/m(2) completed 12 weeks of therapy, and two partial responses were observed., Conclusion: C225 has dose-dependent pharmacokinetics, and doses that achieve saturation of systemic clearance are well tolerated. C225 given in combination with cisplatin has biologic activity at pharmacologically relevant doses.
- Published
- 2000
- Full Text
- View/download PDF
7. Dose-response trial of megestrol acetate in advanced breast cancer: cancer and leukemia group B phase III study 8741.
- Author
-
Abrams J, Aisner J, Cirrincione C, Berry DA, Muss HB, Cooper MR, Henderson IC, Panasci L, Kirshner J, Ellerton J, and Norton L
- Subjects
- Adult, Aged, Antineoplastic Agents adverse effects, Breast Neoplasms mortality, Breast Neoplasms pathology, Disease Progression, Dose-Response Relationship, Drug, Female, Humans, Megestrol Acetate adverse effects, Middle Aged, Prospective Studies, Survival Rate, Antineoplastic Agents administration & dosage, Breast Neoplasms drug therapy, Megestrol Acetate administration & dosage
- Abstract
Purpose: To investigate whether dose escalation of megestrol acetate (MA) improves response rate and survival in comparison with standard doses of MA., Patients and Methods: Three hundred sixty-eight patients with metastatic breast cancer, positive and/or unknown estrogen and progesterone receptors, zero or one prior trial of hormonal therapy, and no prior chemotherapy for metastatic disease were prospectively randomized into three groups. The groups of patients received either MA 160 mg/d (one tablet per day), MA 800 mg/d (five tablets per day), or MA 1,600 mg/d (10 tablets per day)., Results: Patient characteristics were well balanced in the three treatment groups. Three hundred sixty-six patients received treatment and were included in the analyses. The response rates were 23%, 27%, and 27% for the 160-mg, 800-mg, and 1,600-mg arms, respectively. Response duration correlated inversely with dose. Median durations of response were 17 months, 14 months, and 8 months for the 160-mg, 800-mg, and 1,600-mg arms, respectively. No significant differences in the treatment arms were noted for time to disease progression or for survival; survival medians were 28 months (low dose), 24 months (mid dose) and 29 months (high dose). The most frequent and troublesome toxicity, weight gain, was dose-related, with approximately 20% of patients on the two higher-dose arms reporting weight gain of more than 20% of their prestudy weight, compared with only 2% in the 160-mg dose arm., Conclusion: With a median follow-up of 8 years, these results demonstrate no advantage for dose escalation of MA in the treatment of metastatic breast cancer.
- Published
- 1999
- Full Text
- View/download PDF
8. Survival advantage of adjuvant chemotherapy in high-risk node-negative breast cancer: ten-year analysis--an intergroup study.
- Author
-
Mansour EG, Gray R, Shatila AH, Tormey DC, Cooper MR, Osborne CK, and Falkson G
- Subjects
- Adult, Breast Neoplasms mortality, Chemotherapy, Adjuvant, Cyclophosphamide administration & dosage, Female, Fluorouracil administration & dosage, Follow-Up Studies, Humans, Mastectomy, Methotrexate administration & dosage, Middle Aged, Prednisone administration & dosage, Risk, Survival Analysis, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms drug therapy
- Abstract
Purpose: Preliminary analysis showed that adjuvant chemotherapy is effective in improving disease-free survival (DFS) among high-risk breast cancer patients. This report updates the analysis of the high-risk group and reports the results of the low-risk group., Methods: Patients who had undergone a modified radical mastectomy or a total mastectomy with low-axillary sampling, with negative axillary nodes and either an estrogen receptor-negative (ER-) tumor of any size or an estrogen receptor-positive (ER+) tumor that measured > or = 3 cm (high-risk) were randomized to receive six cycles of cyclophosphamide, methotrexate, fluorouracil, and prednisone (CMFP) or no further treatment. Patients with ER+ tumors less than 3 cm (low-risk) were monitored without therapy., Results: DFS and overall survival (OS) at 10 years were 73% and 81%, respectively, among patients who received chemotherapy, as compared with 58% and 71% in the observation group (P=.0006 for DFS and P=.02 for OS). Chemotherapy was beneficial for patients with large tumors, both ER+ and ER-, showing a 10-year DFS of 70% versus 51 % (P=.0009) and OS of 75% versus 65% (P=.06). Ten-year survival was 77% among low-risk patients, 85% among premenopausal patients, and 73% in the postmenopausal group., Conclusion: The observed 37% reduction in risk of recurrence and 34% reduction in mortality risk at 10 years, associated with a 15.4% absolute benefit in disease-free state and 10.1% in survival, reaffirm the role of adjuvant chemohormonal therapy in the management of high-risk node-negative breast cancer. Tumor size remains a significant prognostic factor associated with recurrence and survival in the low-risk group.
- Published
- 1998
- Full Text
- View/download PDF
9. Phase II trial of docetaxel in non-Hodgkin's lymphomas: a study of the Cancer and Leukemia Group B.
- Author
-
Budman DR, Petroni GR, Johnson JL, Cooper MR, Schlossman DM, Barcos M, and Peterson BA
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Phytogenic adverse effects, Docetaxel, Female, Humans, Lymphoma, Non-Hodgkin mortality, Male, Middle Aged, Paclitaxel adverse effects, Paclitaxel therapeutic use, Survival Rate, Antineoplastic Agents, Phytogenic therapeutic use, Lymphoma, Non-Hodgkin drug therapy, Paclitaxel analogs & derivatives, Taxoids
- Abstract
Purpose: To evaluate the new anticancer agent, docetaxel, with a novel mechanism of action in patients with non-Hodgkin's lymphoma International Working Formulation (IWF) A through H, to determine the response rate by histologic group and the toxicities of this agent in this population., Patients and Methods: Sixty-eight patients previously treated for non-Hodgkin's lymphoma with two prior cytotoxic regimens for low-grade and one prior regimen for intermediate-grade lymphoma were entered onto this phase II trial. Central pathologic review was required. Twenty-four IWF A to C and 31 IWF D to H patients with normal hepatic and renal function, performance status (PS) 0 to 2, and adequate hematologic function were eligible. Patients received docetaxel 100 mg/m2 intravenously over 1 hour without corticosteroid premedications every 3 weeks with weekly hematologic monitoring, and tumor assessment every 3 weeks. For grade 3 or 4 hematologic toxicity, the docetaxel dosage was lowered to 75 mg/m2. Patients received a maximum of six cycles of therapy., Results: The major response rate was 13% (95% confidence limits, 3% to 32%) for IWF A to C and 16% (95% confidence limits, 5% to 34%) for IWF D to H; response durations ranged from 1.4 to 20 months. Time to response ranged from 1.3 to 2.8 months. Patients refractory to previous chemotherapy were less apt to respond to docetaxel, but the differences were not statistically different in this small sample size. Twelve percent of IWF A to C and 6% of IWF D to H patients discontinued treatment because of toxicity. The major toxicity was granulocytopenia (grade 3 to 4), which occurred in virtually all patients during the first course of therapy., Conclusion: This study confirms that docetaxel has limited but definite activity in patients with non-Hodgkin's lymphoma and suggests that the previously reported responses with taxanes can not be attributed solely to the use of corticosteroid premedications.
- Published
- 1997
- Full Text
- View/download PDF
10. Phase II trial of suramin, leuprolide, and flutamide in previously untreated metastatic prostate cancer.
- Author
-
Dawson NA, Figg WD, Cooper MR, Sartor O, Bergan RC, Senderowicz AM, Steinberg SM, Tompkins A, Weinberger B, Sausville EA, Reed E, and Myers CE
- Subjects
- Adult, Aged, Antineoplastic Agents, Hormonal administration & dosage, Disease Progression, Drug Administration Schedule, Flutamide administration & dosage, Humans, Leuprolide administration & dosage, Male, Middle Aged, Prostate-Specific Antigen blood, Prostatic Neoplasms immunology, Suramin administration & dosage, Survival Analysis, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Prostatic Neoplasms drug therapy, Prostatic Neoplasms pathology
- Abstract
Purpose: To assess the efficacy and toxicity of suramin, hydrocortisone, leuprolide, and flutamide in previously untreated metastatic prostate cancer., Patients and Methods: Patients with stage D2 and poor-prognosis stage D1 prostate cancer were given suramin on a pharmacokinetically derived dosing schedule to maintain suramin concentrations between 175 and 300 micrograms/mL. Additionally, all patients received flutamide 250 mg orally three times daily, initiated on day 1 and continued until disease progression; depot leuprolide 7.5 mg intramuscularly begun on day 5 and repeated every 4 weeks indefinitely; and replacement doses of hydrocortisone., Results: Fifty patients were entered onto the study: 48 with stage D2 and two with stage D1 disease. The median age was 59 years (range, 42 to 79) and 31 patients had a Karnofsky performance status (KPS) of 100%. Forty-five patients had bone metastases and 25 had measurable soft tissue disease. Forty-one (82%) had severe disease. The overall response rate in 49 assessable patients was three complete responses (CRs) and 30 partial responses (PRs) for an overall response rate of 67%. Eighteen patients have died. The median survival time has not been reached, with a median potential follow-up duration of 44 months. Grade 3 to 4 toxicity was seen in 38% of patients and was predominantly hematologic and reversible., Conclusion: The high response rate and prolonged survival in a poor-prognosis group of patients with metastatic prostate cancer warrant a phase III randomized comparison of this regimen versus hormonal therapy alone. Toxicity was moderate and reversible.
- Published
- 1997
- Full Text
- View/download PDF
11. Pharmacologic variables associated with the development of neurologic toxicity in patients treated with suramin.
- Author
-
Bitton RJ, Figg WD, Venzon DJ, Dalakas MC, Bowden C, Headlee D, Reed E, Myers CE, and Cooper MR
- Subjects
- Adult, Aged, Aged, 80 and over, Humans, Logistic Models, Male, Melanoma blood, Melanoma drug therapy, Middle Aged, Motor Neuron Disease chemically induced, Multivariate Analysis, Prostatic Neoplasms blood, Prostatic Neoplasms drug therapy, Sarcoma blood, Sarcoma drug therapy, Suramin administration & dosage, Suramin pharmacokinetics, Nervous System Diseases chemically induced, Suramin adverse effects
- Abstract
Purpose: To describe pharmacologic variables correlated with the development of neurologic toxicity in patients treated with suramin., Methods: Eighty-one patients were treated with suramin in a phase I study. The rate of drug infusion was continuously adjusted to maintain a preassigned plasma suramin concentration (175, 215, or 275 micrograms/mL) for a fixed duration (2 to 8 weeks)., Results: Eight patients developed grade III/IV neurologic motor impairment (predominantly motor axonal polyneuropathy). All were treated at the 275-micrograms/mL concentration. One patient treated at the 215-micrograms/mL concentration developed grade II motor dysfunction. In addition, seven of nine patients had sensory symptoms. Pharmacologic variables associated with the development of polyneuropathy included total cumulative suramin dose, duration of exposure to plasma concentrations greater than 200 micrograms/mL, and area under the curve (AUC) greater than 200 micrograms/mL., Conclusion: Significant neurologic toxicity can result from therapy with suramin, even when dosing is designed to avoid exposure to plasma concentrations greater than 350 micrograms/mL. Future clinical trials of suramin should be designed in such a way as to limit the total cumulative dose to < or = 157 mg/kg given over a period of > or = 8 weeks, limit the period of exposure to plasma suramin concentrations greater than 200 micrograms/mL to < or = 25 days, and limit the AUC greater than 200 micrograms/mL to < or = 48,000 mg.h/AL.
- Published
- 1995
- Full Text
- View/download PDF
12. Tamoxifen versus high-dose oral medroxyprogesterone acetate as initial endocrine therapy for patients with metastatic breast cancer: a Piedmont Oncology Association study.
- Author
-
Muss HB, Case LD, Atkins JN, Bearden JD 3rd, Cooper MR, Cruz JM, Jackson DV Jr, O'Rourke MA, Pavy MD, and Powell BL
- Subjects
- Administration, Oral, Adult, Aged, Aged, 80 and over, Bone Neoplasms drug therapy, Bone Neoplasms secondary, Breast Neoplasms mortality, Breast Neoplasms pathology, Drug Administration Schedule, Female, Humans, Liver Neoplasms drug therapy, Liver Neoplasms secondary, Medroxyprogesterone Acetate adverse effects, Middle Aged, Prospective Studies, Regression Analysis, Soft Tissue Neoplasms drug therapy, Soft Tissue Neoplasms secondary, Survival Analysis, Tamoxifen adverse effects, Breast Neoplasms drug therapy, Medroxyprogesterone Acetate administration & dosage, Tamoxifen administration & dosage
- Abstract
Purpose: To determine in a prospective randomized trial whether high-dose orally administered medroxy-progesterone acetate (MPA) was superior to tamoxifen in patients with recurrent or metastatic breast cancer who had received no prior endocrine therapy in either the adjuvant or advanced setting., Patients and Methods: Patients initially received either tamoxifen 20 mg/d orally or MPA 1 g/d orally. At the time of disease progression, patients were crossed over to the other regimen. Eligibility required patients to be age > or = 18 years, performance status 0 to 3, and estrogen receptor (ER)- or progesterone receptor (PR)-positive or unknown., Results: One hundred eighty-two eligible patients were entered and 166 were assessable for response. Complete plus partial response rates for tamoxifen and MPA were 17% and 34%, respectively (P = .01). Patients with bone metastases had a significantly higher partial response rate with MPA compared with tamoxifen (33% v 13%). Median time to treatment failure was 5.5 months for tamoxifen and 6.3 months for MPA (P = .48). The median survival duration was 24 months for tamoxifen and 33 months for MPA (P = .09). Multivariate analysis showed that treatment significantly influenced response rate, but not time to treatment failure or survival. After treatment failure following MPA, six of 42 patients (14%) treated with tamoxifen responded, compared with six of 49 (12%) treated with MPA following tamoxifen. Both agents were associated with minimal toxicity, but 35% of patients on MPA gained more than 20 lb as opposed to only 2% on tamoxifen., Conclusion: In this trial, initial treatment with MPA of endocrine-naive metastatic breast cancer patients was associated with a significantly higher response rate but not with improvement in time to treatment failure or survival, when compared with initial treatment with tamoxifen. Further randomized trials in patients with bone metastases are warranted to determine if high-dose progestin therapy is superior to tamoxifen in these patients.
- Published
- 1994
- Full Text
- View/download PDF
13. Adaptive control with feedback of suramin using intermittent infusions.
- Author
-
Figg WD, Stevens JA, and Cooper MR
- Subjects
- Drug Administration Schedule, Humans, Infusions, Intravenous, Male, Prostatic Neoplasms metabolism, Suramin administration & dosage, Suramin pharmacokinetics
- Published
- 1994
- Full Text
- View/download PDF
14. Trimetrexate in malignant mesothelioma: A Cancer and Leukemia Group B Phase II study.
- Author
-
Vogelzang NJ, Weissman LB, Herndon JE 2nd, Antman KH, Cooper MR, Corson JM, and Green MR
- Subjects
- Adult, Aged, Female, Humans, Male, Middle Aged, Survival Analysis, Treatment Outcome, Trimetrexate adverse effects, Mesothelioma drug therapy, Trimetrexate therapeutic use
- Abstract
Purpose: Folic acid antagonists are reported to have activity against mesothelioma. The Cancer and Leukemia Group B (CALGB) undertook this phase II study of the new antifolate, trimetrexate (TMTX), to evaluate its response rate and toxicity in chemotherapy-naive patients with malignant mesothelioma., Patients and Methods: Fifty-two patients were accrued to this protocol. Because of concerns about TMTX toxicity in patients with malignant effusions and/or hypoalbuminemia, the first 17 patients were treated at a dose of 6 mg/m2 daily for 5 days every 21 days. Because minimal toxicity was observed, the subsequent 35 patients were treated at a dose of 10 mg/m2., Results: Two of 17 patients (12%) in the 6-mg/m2 treatment group had a partial response (PR) and four of 34 eligible patients (12%) in the 10-mg/m2 treatment group had a PR or regression (R) of assessable disease. No patient achieved a complete response (CR). Median survival durations were 5.0 and 8.9 months in the 6- and 10-mg/m2 treatment groups, respectively, while the 2-year survival rates were identical at 18%. At the 10-mg/m2 dose, toxicity was tolerable, with one toxic death from sepsis and a 12% rate of grade 4 thrombocytopenia and granulocytopenia., Conclusion: In this large trial, TMTX showed minor activity in the treatment of malignant mesothelioma. Myelosuppression was mild and dose-related. Future studies of higher doses of TMTX should be considered.
- Published
- 1994
- Full Text
- View/download PDF
15. Effect of megestrol acetate on quality of life in a dose-response trial in women with advanced breast cancer. The Cancer and Leukemia Group B.
- Author
-
Kornblith AB, Hollis DR, Zuckerman E, Lyss AP, Canellos GP, Cooper MR, Herndon JE 2nd, Phillips CA, Abrams J, and Aisner J
- Subjects
- Appetite drug effects, Dose-Response Relationship, Drug, Female, Humans, Linear Models, Megestrol adverse effects, Megestrol therapeutic use, Megestrol Acetate, Middle Aged, Multivariate Analysis, Treatment Outcome, Weight Gain drug effects, Breast Neoplasms drug therapy, Breast Neoplasms psychology, Megestrol analogs & derivatives, Quality of Life
- Abstract
Purpose: The impact of the side effects of megestrol acetate on the quality of life of noncachectic women with advanced breast cancer was studied in a dose-response clinical trial of the Cancer and Leukemia Group B (CALGB 8741). Side effects of appetite increase and weight gain at higher doses were predicted to have a negative effect on quality of life., Patients and Methods: Stage IV breast cancer patients were randomized to receive either 160, 800, or 1,600 mg/d of megestrol acetate. Quality of life was assessed in 131 patients at trial entry and at 1 and 3 months while on treatment, by telephone interview, using the following measures: the Functional Living Index-Cancer (FLIC), Rand Functional Limitations Scale, Rand Mental Health Inventory (MHI), the Body Image Subscale, and linear analog scales of drug side effects., Results: At 3 months, women treated with 160 mg/d reported less severe side effects (P < .0005), better physical functioning (FLS, P < .0005), less psychologic distress (MHI, P = .008), and an improvement in overall quality of life (FLIC, P = .003) from the time of study entry as compared with those treated with 1,600 mg/d. Patients who received the 800-mg/d dose fell between the low- and high-dose arms in reported intensity of drug side effects, but responded similarly to those in the 160-mg/d group in terms of physical functioning, psychologic distress, and overall quality of life., Conclusion: Unless additional follow-up data demonstrate a survival advantage at higher doses, the 160-mg/d dose is optimal, achieving maximal treatment effect with the fewest side effects and better quality of life.
- Published
- 1993
- Full Text
- View/download PDF
16. AMOPLACE treatment of intermediate-grade and high-grade malignant lymphoma: a Cancer and Leukemia Group B study.
- Author
-
Parker BA, Santarelli M, Green MR, Anderson JR, Cooper MR, Case D Jr, Barcos M, Peterson BA, and Gottlieb AJ
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Drug Administration Schedule, Female, Humans, Male, Middle Aged, Survival Analysis, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Lymphoma, Non-Hodgkin drug therapy
- Abstract
Purpose: In an attempt to improve the efficacy of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy for intermediate-grade and high-grade non-Hodgkin's lymphomas, a phase II evaluation of a regimen consisting of Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), methotrexate, Oncovin (vincristine; Eli Lilly Co, Indianapolis, IN), prednisone, leucovorin, cytarabine (ara-c), cyclophosphamide, and etoposide (AMOPLACE) was conducted. This regimen includes three additional agents not found in CHOP, uses weekly doses of alternating myelosuppressive and nonmyelosuppressive drugs, and incorporates most single agents active against diffuse lymphomas., Patients and Methods: Ninety-one previously untreated patients were enrolled and 60 patients were confirmed eligible after central pathology review. Fifty-eight percent of patients had diffuse large-cell lymphoma (DLCL), 83% had stage III or IV disease, and 45% had B symptoms., Results: Patients were treated with six to eight cycles of AMOPLACE and analyzed for response and survival. With a median follow-up of 48 months, complete responses (CRs) were seen in 68% of all patients with failure-free survival (FFS) and overall survival (OS) estimates at 4 years of 45% and 54%. In the DLCL subset, the CR rate was 69% and FFS and OS estimates at 4 years were 49% and 60%, respectively. The major toxicity was myelosuppression, with 73% of patients having WBC nadirs less than 1,000/microL; two treatment-related deaths occurred., Conclusion: We conclude that AMOPLACE is associated with CR and OS rates comparable with those of other third-generation regimens.
- Published
- 1993
- Full Text
- View/download PDF
17. A randomized clinical trial comparing melphalan/prednisone with or without interferon alfa-2b in newly diagnosed patients with multiple myeloma: a Cancer and Leukemia Group B study.
- Author
-
Cooper MR, Dear K, McIntyre OR, Ozer H, Ellerton J, Canellos G, Bernhardt B, Duggan D, Faragher D, and Schiffer C
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols adverse effects, Female, Humans, Interferon alpha-2, Interferon-alpha administration & dosage, Male, Melphalan administration & dosage, Middle Aged, Prednisone administration & dosage, Recombinant Proteins, Survival Analysis, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Multiple Myeloma drug therapy
- Abstract
Purpose: This clinical trial was designed to compare the effectiveness of the standard melphalan and prednisone regimen to that of melphalan, prednisone, and interferon in patients with untreated multiple myeloma., Patients and Methods: Between October 1985 and March 1988, 278 patients were accrued to a multi-institutional, randomized clinical trial. Responding patients were treated for 2 years before termination of therapy., Results: After a median follow-up of 23 months, the overall remission rate for the melphalan/prednisone treatment group was 44% compared with 33% for the group receiving melphalan/prednisone/interferon alfa-2b. The durations of response and survival were identical for the two treatment groups. Median survival was 3.17 years on melphalan/prednisone treatment and 3.0 years on melphalan/prednisone/interferon alfa-2b treatment. Both hematologic and nonhematologic toxicities were greater in the melphalan/prednisone/interferon alfa-2b treatment group, but were usually of a mild or moderate degree and did not interfere with the completion of therapy. The frequency of deaths in the two treatment groups attributable to the treatment itself was similar., Conclusion: This study shows no advantage to the concomitant delivery of interferon alfa-2b with standard melphalan and prednisone as initial treatment for patients with multiple myeloma.
- Published
- 1993
- Full Text
- View/download PDF
18. Mood and clinical status in patients with multiple myeloma.
- Author
-
Silberfarb PM, Anderson KM, Rundle AC, Holland JC, Cooper MR, and McIntyre OR
- Subjects
- Adult, Aged, Female, Humans, Male, Middle Aged, Prognosis, Regression Analysis, Survival Analysis, Treatment Outcome, Affect, Multiple Myeloma psychology
- Abstract
Two hundred ninety patients with a recent diagnosis of multiple myeloma were studied psychologically at the time of initial treatment. Physician- and patient-completed psychosocial scales were correlated with physical variables used to measure tumor load and physical status. A logistic regression model was used to analyze objective response to treatment. Indirect measures of response to treatment were obtained, and factors influencing survival duration were studied using a Cox regression model. If physical variables were controlled, there were no significant correlations between psychologic scores on entry and response to treatment or survival duration. Thus, the notion that mood influences disease outcome once the disease process has begun in patients with multiple myeloma is not supported by this data set.
- Published
- 1991
- Full Text
- View/download PDF
19. High- versus standard-dose megestrol acetate in women with advanced breast cancer: a phase III trial of the Piedmont Oncology Association.
- Author
-
Muss HB, Case LD, Capizzi RL, Cooper MR, Cruz J, Jackson D, Richards F 2nd, Powell BL, Spurr CL, and White D
- Subjects
- Adult, Aged, Aged, 80 and over, Breast Neoplasms mortality, Breast Neoplasms pathology, Cardiovascular Diseases etiology, Female, Humans, Megestrol administration & dosage, Megestrol adverse effects, Megestrol Acetate, Middle Aged, Survival Rate, Weight Gain, Breast Neoplasms drug therapy, Megestrol analogs & derivatives
- Abstract
One hundred seventy-two patients with advanced breast cancer were randomized to receive oral standard-dose megestrol acetate (MA), 160 mg/d or high-dose MA, 800 mg/d. All but two patients had one prior trial of tamoxifen therapy for either metastatic disease (74%) or as adjuvant treatment (26%). Pretreatment characteristics were similar for both arms. High-dose MA resulted in a superior complete plus partial response rate (27% v 10%, P = .005), time to treatment failure (median, 8.0 v 3.2 months, P = .019), and survival (median, 22.4 v 16.5 months, P = .04) when compared with standard-dose therapy. These differences remained significant after adjustment for other covariates. Thirty-four patients were given high-dose MA after failure of standard-dose MA treatment, and none responded. Weight gain was the most distressing side effect, with 13% of standard-dose and 43% of high-dose patients gaining more than 20 lbs. Four major cardiovascular events occurred in patients receiving high-dose treatment and one in patients given standard doses. Other toxicity was modest. High-dose MA may represent a significant improvement in secondary endocrine therapy for advanced breast cancer patients refractory to initial endocrine treatment, but its use on a regular basis should be reserved until these results are confirmed by other clinical trials.
- Published
- 1990
- Full Text
- View/download PDF
20. Peripheral neuropathy after high-dose cytosine arabinoside, daunorubicin, and asparaginase consolidation for acute nonlymphocytic leukemia.
- Author
-
Powell BL, Capizzi RL, Lyerly ES, and Cooper MR
- Subjects
- Acute Disease, Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Asparaginase administration & dosage, Cytarabine administration & dosage, Daunorubicin administration & dosage, Female, Humans, Male, Middle Aged, Antineoplastic Combined Chemotherapy Protocols toxicity, Leukemia, Monocytic, Acute drug therapy, Leukemia, Myeloid, Acute drug therapy, Peripheral Nervous System Diseases chemically induced
- Abstract
Two patients with acute nonlymphocytic leukemia (ANLL) developed peripheral motor and sensory neuropathies after consolidation chemotherapy with high-dose cytosine arabinoside (ara-C), daunorubicin, and asparaginase. Evidence for ara-C and daunorubicin-induced peripheral neuropathies is reported. Despite the frequent use of these agents, only two cases of peripheral neuropathy after systemic therapy have been previously described; neurotoxic effects may be potentiated and become clinically important when the three drugs are used in combination.
- Published
- 1986
- Full Text
- View/download PDF
21. Single, sequential, and multiple alkylating agent therapy for multiple myeloma: a CALGB Study.
- Author
-
Cooper MR, McIntyre OR, Propert KJ, Kochwa S, Anderson K, Coleman M, Kyle RA, Prager D, Rafla S, and Zimmer B
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Carmustine administration & dosage, Carmustine adverse effects, Clinical Trials as Topic, Cyclophosphamide administration & dosage, Cyclophosphamide adverse effects, Doxorubicin administration & dosage, Doxorubicin adverse effects, Drug Hypersensitivity, Female, Humans, Leukocyte Count drug effects, Male, Melphalan administration & dosage, Melphalan adverse effects, Middle Aged, Multiple Myeloma mortality, Myeloma Proteins blood, Myeloma Proteins urine, Platelet Count drug effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Multiple Myeloma drug therapy
- Abstract
Four intravenous (IV) alkylating agent regimens were tested in 615 previously untreated patients with multiple myeloma. Patients were randomized to receive melphalan, cyclophosphamide, and carmustine in combination (MCBP), sequentially (Seq-MCBP), or in combination with doxorubicin (MCBPA). The fourth group received IV melphalan (MP) as the only alkylating agent. All groups received a tapering dose of prednisone. Toxicity was similar for all regimens although the nadir of cytopenia was reached more quickly for the regime including melphalan only. Response as measured by reduction in myeloma protein or other parameters were similar for the four treatments. Survival was significantly poorer for the group receiving the alkylating agents in sequence. The survival of high tumor cell load patients who were azotemic was better in the groups treated with IV MP or with the combination of IV MCBP. In view of the simplicity and probable cost savings attached to single-agent treatment, a melphalan/prednisone regimen should be considered as initial therapy for all patients with myeloma.
- Published
- 1986
- Full Text
- View/download PDF
22. A phase II study of recombinant alpha interferon in patients with recurrent or metastatic breast cancer.
- Author
-
Muss HB, Kempf RA, Martino S, Rudnick SA, Greiner J, Cooper MR, Decker D, Grunberg SM, Jackson DV, and Richards F 2nd
- Subjects
- Adult, Aged, Breast Neoplasms pathology, Confusion chemically induced, DNA, Recombinant, Drug Administration Schedule, Drug Evaluation, Female, Humans, Influenza, Human chemically induced, Injections, Intravenous, Injections, Subcutaneous, Interferon Type I administration & dosage, Interferon Type I adverse effects, Middle Aged, Neoplasm Metastasis, Neoplasm Recurrence, Local, Breast Neoplasms therapy, Interferon Type I therapeutic use
- Abstract
Thirty-three patients with advanced breast cancer were treated with a recombinant alpha interferon (rIFN-alpha 2). All patients were ambulatory (performance status greater than or equal to 50 Karnofsky scale) and almost all had received previous chemotherapy. Large intravenous dosages of 30 to 50 X 10(6) IU/m2 were given for five consecutive days every two to three weeks to 22 patients and smaller subcutaneous dosage of 2 X 10(6) IU/m2 three times a week to 11 patients. No complete or partial responses were seen. Two patients had stable disease and the remainder progressed. Flu-like syndromes were seen in all patients. Nausea, vomiting, and anorexia were frequent. Hypotension and confusion were noted in six and five patients, respectively. Life-threatening leukopenia was noted in two patients receiving intravenous dosage and thrombocytopenia was noted in one; no sepsis or bleeding complications were noted. In this study, a highly purified and biologically active rIFN-alpha 2 was not associated with activity in previously treated women with metastatic breast cancer.
- Published
- 1984
- Full Text
- View/download PDF
23. Combination chemotherapy (5-fluorouracil, methyl-CCNU, mitomycin C) versus 5-fluorouracil alone for advanced previously untreated colorectal carcinoma. A phase III study of the Piedmont Oncology Association.
- Author
-
Richards F 2nd, Case LD, White DR, Muss HB, Spurr CL, Jackson DV, Cooper MR, Zekan P, Cruz J, and Stuart JJ
- Subjects
- Adolescent, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols toxicity, Clinical Trials as Topic, Drug Administration Schedule, Female, Fluorouracil administration & dosage, Fluorouracil toxicity, Follow-Up Studies, Humans, Male, Middle Aged, Mitomycin, Mitomycins administration & dosage, Semustine administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Colonic Neoplasms drug therapy, Fluorouracil therapeutic use, Rectal Neoplasms drug therapy
- Abstract
One-hundred thirty eligible patients with advanced colorectal carcinoma who had received no prior chemotherapy were randomized to either methyl-CCNU, 70 mg/m2 orally every 6 weeks on day 1, mitomycin C, 10 mg/m2 intravenously every 6 weeks on day 1, and 5-fluorouracil (5-FU), 400 mg/m2 intravenously weekly--(MMF)--or 5-FU, 600 mg/m2 intravenously weekly (5-FU). One hundred twenty-six patients are evaluable for response. Of 62 patients treated with MMF, one (2%) achieved complete remission, and three (5%) attained partial remission. Of 64 patients treated with 5-FU, two (3%) achieved complete remission, and eight (13%) attained partial remission. The median survival for patients receiving MMF was 9.5 months compared with 10.3 months for patients receiving 5-FU. The survival distributions for the two regimens were not significantly different, either unadjusted or adjusted for pretreatment characteristics. Performance status and lactic dehydrogenase (LDH) were both significantly associated with survival. Patients with liver metastases only and normal liver function tests had a median survival of 19.8 months and a 40% response rate. This randomized phase III trial did not show any therapeutic advantage for MMF compared to 5-FU therapy alone in advanced colorectal cancer. In addition, hematologic toxicity was significantly greater with the combination (MMF) regimen.
- Published
- 1986
- Full Text
- View/download PDF
24. Phase II study of recombinant alpha-2 interferon in resistant multiple myeloma.
- Author
-
Costanzi JJ, Cooper MR, Scarffe JH, Ozer H, Grubbs SS, Ferraresi RW, Pollard RB, and Spiegel RJ
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, DNA, Recombinant, Drug Administration Schedule, Drug Evaluation, Female, Hematologic Diseases etiology, Humans, Interferon Type I adverse effects, Male, Middle Aged, Recurrence, Interferon Type I therapeutic use, Multiple Myeloma therapy
- Abstract
A multicenter phase II study of INTRON, recombinant alpha-2 interferon (Schering Corp, Kenilworth, NJ), in patients with relapsing or refractory myeloma was initiated. Patients received either intravenous therapy for two weeks followed by subcutaneous therapy or subcutaneous dosing from initiation of treatment. Of 38 evaluable patients, 19 were refractory and 19 had relapsed at entry. Twenty-five of 38 had received prior treatment with multiple drugs. Responses were seen among 2/19 refractory patients and 5/19 relapsing patients. Three of seven responders continue to respond for more than one year while receiving maintenance therapy. Most patients experienced improvement in bone pain, and one patient, with a complete response, had healing of bone lesions. Survival curves show a statistically significant improvement in survival for responders v nonresponders. INTRON was well-tolerated with only four patients discontinuing treatment due to adverse effects. Thirty-two percent of patients had hematologic toxicity requiring dose adjustment; however, there was no evidence of cumulative hematologic toxicity. No patients developed serum neutralizing factors to interferon. Additional trials are warranted to study the activity of INTRON in previously untreated patients.
- Published
- 1985
- Full Text
- View/download PDF
25. Vincristine and prednisone prolong the survival of patients receiving intravenous or oral melphalan for multiple myeloma: Cancer and Leukemia Group B experience.
- Author
-
Cornwell GG 3rd, Pajak TF, Kochwa S, McIntyre OR, Glowienka LP, Brunner K, Rafla S, Coleman M, Cooper MR, and Henderson E
- Subjects
- Carmustine administration & dosage, Clinical Trials as Topic, Drug Administration Schedule, Female, Humans, Lomustine administration & dosage, Male, Melphalan administration & dosage, Middle Aged, Multiple Myeloma mortality, Prednisone administration & dosage, Random Allocation, Vincristine administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Multiple Myeloma drug therapy
- Abstract
A total of 589 patients with previously untreated multiple myeloma were randomized to receive daily oral melphalan, pulse-dose intravenous (IV) melphalan, carmustine (BCNU), or lomustine (CCNU). All patients received an initial tapering course of prednisone (Pred). During week 22 (day 154), patients were randomized to receive or not to receive additional therapy with vincristine (VCR) (1 mg/m2) and prednisone (0.6 mg/kg/d for seven days) at 8-week intervals. The influence of VCR/Pred was determined in 302 patients who remained on study beyond 22 weeks after initial therapy. VCR/Pred converted a significant percentage of nonresponders to responders in patients treated with melphalan (55% v 19%, P = .002), but not in patients treated with a nitrosourea (48% v 23%, P = .06). Survival beyond week 22 was significantly longer following the addition of VCR/Pred in patients receiving melphalan (median, 35.3 months v 27.0 months; P = .003) but not in patients receiving BCNU or CCNU (median, 28.1 months v 26.2 months; P = .91). These differences were seen both for oral and IV melphalan. A trend for beneficial effect of VCR/Pred was definitely seen in the good-risk patients (P = .03) but only suggestive for poor-risk patients (P = .12). Following adjustment for VCR/Pred effects, there were no differences in the survival of patients receiving any of the four initial treatments.
- Published
- 1988
- Full Text
- View/download PDF
26. Improvement of long-term survival in extensive small-cell lung cancer.
- Author
-
Jackson DV Jr, Case LD, Zekan PJ, Powell BL, Caldwell RD, Bearden JD, Nelson EC, Muss HB, Cooper MR, and Richards F 2nd
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Carcinoma, Small Cell mortality, Clinical Trials as Topic, Cyclophosphamide administration & dosage, Dactinomycin administration & dosage, Doxorubicin administration & dosage, Female, Humans, Lung Neoplasms mortality, Male, Middle Aged, Podophyllotoxin administration & dosage, Prognosis, Random Allocation, Vincristine administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Small Cell drug therapy, Lung Neoplasms drug therapy
- Abstract
The effect of adding the epipodophyllotoxin etoposide (VP-16-213) to a standard chemotherapy regimen for patients with extensive stage small-cell lung cancer was evaluated during a randomized trial. Chemotherapy consisted of vincristine, doxorubicin, and cyclophosphamide (VAC) alone or with etoposide (EVAC). Of 139 patients enrolled, 136 patients were eligible for study and all but five were evaluable for response. The overall objective response was 46% in the VAC group v 70% in the etoposide-treated group (P = .008) with complete response (CR) rates of 12% v 29%, respectively (P = .030). Although the time to the observation of disease progression was significantly longer in the group of patients receiving etoposide (9.6 v 6.5 months, P = .010), overall survival was similar; this was probably due to administration of other agents including etoposide at the time of VAC failure. However, there were noteworthy differences in long-term (greater than or equal to 2 year) survival. Whereas only four (6%) patients treated with VAC lived 2 years, 11 (16%) of the etoposide-treated group did so (P = .100). Two-year failure-free survival was attained in one (2%) of the VAC patients and eight (11%) of the patients treated with etoposide (P = .034). Long-term survivorship, heretofore usually reported in patients with limited stage disease after a variety of treatments, may be possible with this drug combination in the setting of extensive disease.
- Published
- 1988
- Full Text
- View/download PDF
27. Tamoxifen rechallenge: response to tamoxifen following relapse after adjuvant chemohormonal therapy for breast cancer.
- Author
-
Muss HB, Smith LR, and Cooper MR
- Subjects
- Adult, Aged, Breast Neoplasms pathology, Female, Humans, Middle Aged, Neoplasm Metastasis, Receptors, Estrogen analysis, Receptors, Progesterone analysis, Breast Neoplasms drug therapy, Neoplasm Recurrence, Local drug therapy, Tamoxifen therapeutic use
- Abstract
Two-hundred seventy-three node-positive primary breast cancer patients with positive estrogen or progesterone receptors were placed on a short-term chemohormonal adjuvant program that included tamoxifen. At present, 64 have relapsed, 19 of whom have been rechallenged with tamoxifen after disease-free intervals (DFI) ranging from 0.4 to 4.4 years. Most patients had only one site of disease recurrence. Two patients have achieved complete remission (CR) and three partial remission (PR) for a CR and PR rate of 26% (95% confidence interval for CR and PR is 9% to 51%). Duration of response has ranged from 3 to 17+ months. Patients who receive short-term adjuvant therapy with tamoxifen and who relapse may respond to tamoxifen rechallenge. In this series, the response rate to tamoxifen rechallenge was similar to the response rate for patients unselected for estrogen receptor status receiving first-line endocrine therapy for breast cancer relapse.
- Published
- 1987
- Full Text
- View/download PDF
28. Megestrol acetate versus tamoxifen in advanced breast cancer: 5-year analysis--a phase III trial of the Piedmont Oncology Association.
- Author
-
Muss HB, Wells HB, Paschold EH, Black WR, Cooper MR, Capizzi RL, Christian R, Cruz JM, Jackson DV, and Powell BL
- Subjects
- Adult, Aged, Aged, 80 and over, Clinical Trials as Topic, Female, Humans, Megestrol adverse effects, Megestrol therapeutic use, Megestrol Acetate, Middle Aged, Neoplasm Metastasis, Random Allocation, Remission Induction, Tamoxifen adverse effects, Breast Neoplasms drug therapy, Megestrol analogs & derivatives, Tamoxifen therapeutic use
- Abstract
One hundred thirty-eight patients with recurrent or metastatic breast cancer were randomized to receive megestrol acetate 40 mg orally four times daily or tamoxifen 10 mg orally twice a day. Upon treatment failure patients were crossed over to the alternate treatment. Eligibility required that either the estrogen receptor (ER) or progesterone receptor (PR) be positive or that both values be unknown, and that the patients be at least 2 years post-spontaneous menopause or over 50 years of age. Pretreatment characteristics including performance status (PS), disease-free interval (DFI), receptor status, and prior treatment were similar for both groups. Only three patients had previous hormonal therapy while one third had prior chemotherapy. Objective response was determined using strict International Union Against Cancer (UICC) criteria. Seventeen of 61 patients achieved complete response (CR) or partial response (PR) on megestrol (28%) while 20 of 64 patients achieved CR or PR on tamoxifen (31%). Responses of skin and bone lesions were similar for both agents; however, more patients with visceral disease responded to tamoxifen. Response did not correlate with the level of ER or PR but was correlated with age. Both unadjusted and adjusted analysis of time to progression and adjusted analysis (for pretreatment variables) of survival showed significant differences favoring tamoxifen. Six of 44 patients (14%) crossed from megestrol to tamoxifen achieved CR or PR while only two of 38 patients (5%) crossed from tamoxifen to megestrol achieved response. Only one of the original patients randomized to megestrol remains on study, while 12 patients still remain on tamoxifen. These data indicate similar response rates for megestrol and tamoxifen; however, time to progression and overall survival significantly favor tamoxifen when used as first-line therapy in this trial.
- Published
- 1988
- Full Text
- View/download PDF
29. The effects of prior radiation therapy and age on the frequency and duration of complete remission among various four-drug treatments for advanced Hodgkin's disease.
- Author
-
Cooper MR, Pajak TF, Gottlieb AJ, Glicksman AS, Nissen N, Richards F 2nd, Bloomfield C, and Holland JF
- Subjects
- Adult, Age Factors, Antineoplastic Combined Chemotherapy Protocols adverse effects, Clinical Trials as Topic, Combined Modality Therapy, Cyclophosphamide administration & dosage, Female, Hodgkin Disease radiotherapy, Humans, Lomustine administration & dosage, Male, Mechlorethamine administration & dosage, Middle Aged, Neoplasm Staging, Prednisolone administration & dosage, Prednisone administration & dosage, Procarbazine administration & dosage, Random Allocation, Recurrence, Retrospective Studies, Risk, Time Factors, Vinblastine administration & dosage, Vincristine administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hodgkin Disease drug therapy
- Abstract
The current report examines the clinical response observed in 137 patients with advanced Hodgkin's disease who had relapsed from an initial complete response following radiation therapy (RTF) in comparison to 280 patients with no prior therapy (NPT). Patients were prospectively randomized to therapy with a four-drug combination chemotherapy program to determine whether CCNU and/or vinblastine are more effective than mechlorethamine and/or vincristine when combined with procarbazine and prednisone. The frequency of complete remission (CR) was 75% for the RTF group compared to 60% of those with NPT (P = .005). In the RTF group, those patients receiving a nitrosourea (CCNU) had a significantly greater CR frequency than those receiving mechlorethamine (P = .006). Significant risk factors favoring longer duration of remission were age less than 40 (P = .005), the absence of splenic involvement (P = .007), and the use of CCNU-containing programs (P = .015). The advantage for CCNU-containing programs was seen only in patients less than 40 years of age. In this study, the strongest factors favorably affecting response to therapy were prior RTF, age less than 40 years, and treatment with a nitrosourea (CCNU).
- Published
- 1984
- Full Text
- View/download PDF
30. Single agent vincristine by infusion in refractory multiple myeloma.
- Author
-
Jackson DV, Case LD, Pope EK, White DR, Spurr CL, Richards F 2nd, Stuart JJ, Muss HB, Cooper MR, and Black WR
- Subjects
- Adult, Aged, Drug Evaluation, Female, Hematologic Diseases chemically induced, Humans, Infusions, Parenteral, Intestinal Obstruction chemically induced, Male, Middle Aged, Multiple Myeloma pathology, Nausea chemically induced, Peripheral Nervous System Diseases chemically induced, Vincristine adverse effects, Vincristine blood, Multiple Myeloma drug therapy, Vincristine therapeutic use
- Abstract
A phase 2 trial of vincristine infusion was conducted in a group of 21 patients with refractory multiple myeloma. Patients were generally heavily pretreated with radiotherapy and chemotherapy. Vincristine was given intravenously (IV) as a 0.5 mg bolus and followed immediately by infusion of 0.25 to 0.50 mg/m2/d for 5 days. Courses were repeated every 3 weeks in the absence of disease progression or prohibitive toxicity. Objective responses (partial) were noted in two patients (10%), both of whom were administered 0.5 mg/m2/d infusions. Response durations were brief (2.2 and 1.2 months). Toxicity consisted of neurotoxicity and myelosuppression. In addition to the occurrence of paresthesias and myalgias, ileus (two cases) and moderately severe loss of motor function (two cases) were observed. The mean lowest WBC count following treatment was 2.67 X 10(3)/microL v 3.96 X 10(3)/microL pretreatment (P = .008). The mean lowest platelet count was 75.0 X 10(3)/microL v 106.8 X 10(3)/microL pretreatment (P = .008). Vincristine infusion appears to have limited activity in the treatment of refractory multiple myeloma. Additionally, response durations were short lived and toxicity, both neurologic and hematologic, was appreciable.
- Published
- 1985
- Full Text
- View/download PDF
31. Synergy between high-dose cytarabine and asparaginase in the treatment of adults with refractory and relapsed acute myelogenous leukemia--a Cancer and Leukemia Group B Study.
- Author
-
Capizzi RL, Davis R, Powell B, Cuttner J, Ellison RR, Cooper MR, Dillman R, Major WB, Dupre E, and McIntyre OR
- Subjects
- Arabinofuranosyluracil pharmacology, Humans, Leukemia, Myeloid, Acute mortality, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Asparaginase administration & dosage, Cytarabine administration & dosage, Leukemia, Myeloid, Acute drug therapy
- Abstract
One hundred ninety-five adult patients with refractory or first relapse acute myelogenous leukemia (AML) were randomly assigned to receive high-dose cytarabine (HiDAC), 3 g/m2 as a three-hour intravenous (IV) infusion every 12 hours for four doses, followed by 6,000 IU/m2 asparaginase (ASNase) administered at hour 42, or HiDAC without ASNase. Treatment was repeated on day 8. The median patient age was 52 years. There was an overall superior complete remission (CR) rate for HiDAC/ASNase (40%) v HiDAC (24%), P = .02. Subset analysis according to prior response and age showed the following CR rates: 54% from HiDAC/ASNase treatment of refractory AML in patients less than 60 years, and 31% in patients greater than 60 years; CR from HiDAC in the same refractory groups were 18% (less than 60) and 0% (greater than 60); 37% from HiDAC/ASNase treatment of relapsed AML in patients less than 60 years, and 43% in patients greater than 60 years; CRs from HiDAC in the same relapsed groups were 33% (less than 60) and 21% (greater than 60). Toxicity in the two treatment arms was comparable and consisted primarily of leukopenia, thrombocytopenia, mild hepatic dysfunction, diarrhea, conjunctivitis and serositis, and hyperglycemia. There was only one case of transient cerebellar toxicity and no cutaneous toxicity. Median time to full hematologic recovery was 5 weeks. There was an overall survival benefit for patients treated with HiDAC/ASNase (19.6 weeks) compared with HiDAC (15.9 weeks), P = .046, primarily attributable to effects in refractory patients. Median time to failure for refractory patients who achieved CR was 38.5 weeks with HiDAC/ASNase, and 13.3 weeks for those treated with HiDAC. For relapsed patients in CR from HiDAC/ASNase the median time to failure was 17.7 weeks and 18.3 weeks for HiDAC. The overall 42% CR rate from HiDAC/ASNase v 12% from HiDAC in patients with refractory AML indicates that HiDAC/ASNase is not cross-resistant with standard-dose cytarabine (SDAC) and anthracyclines. We conclude that HiDAC/ASNase has substantial activity in poor-prognosis AML and that this combination warrants further trials in earlier stage disease.
- Published
- 1988
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.