Escalated dosages of methotrexate, vinblastine, doxorubicin, and cisplatin plus recombinant human granulocyte colony-stimulating factor in advanced urothelial carcinoma

An eastern cooperative oncology group trial

Patrick Loehrer, Paul Elson, Robert Dreicer, Richard Hahn, Craig R. Nichols, Richard Williams, Lawrence Einhorn

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Abstract

Purpose: This multicenter cooperative group phase I/ II trial evaluated the toxicity and efficacy of escalated dosages of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) with recombinant human granulocyte colony-stimulating factor (rhG-CSF) in patients with advanced urothelial carcinoma. Patients and Methods: From November 1990 through October 1991, 35 patients with advanced urothelial cancer previously untreated with chemotherapy were treated with escalated dosages of M-VAC (M-VACII). In patients with prior pelvic radiotherapy, standard M-VAC (M-VACI) was administered plus rhG-CSF. For other patients, M-VACII dosages were methotrexate 40 mg/m2 (days 1, 15, and 22), vinblastine 4 mg/m2 (days 2, 15, and 22), doxorubicin 40 mg/m2 (day 2), and cisplatin 100 mg/m2 (day 2). In addition, rhG-CSF was administered at a dosage of 300 μg subcutaneously on days 4 to 11. Cycles were repeated every 4 weeks. For patients who tolerated the first course of therapy, subsequent escalation by 25% of all drugs was performed. Results: Six complete responses and 15 partial responses were observed (60%; 95% confidence interval, 42% to 76%). The median duration of response was 4.6 months, and the median survival time was 9.4 months (range, 0.5 to 23.5+). Twenty-eight of 35 patients experienced grade 3 or 4 leukopenia, including 14 patients who developed fever associated with neutropenia. Eight (23%) early deaths were observed. Conclusion: This regimen (M-VACII) with escalated dosages of M-VAC was associated with significant toxicity and had no apparent benefit over M-VAC1 therapy with regard to complete response rate or survival. Further evaluation of the dose-intensity of the components of this regimen in this disease is likely to be of limited benefit to patients.

Original languageEnglish
Pages (from-to)483-488
Number of pages6
JournalJournal of Clinical Oncology
Volume12
Issue number3
StatePublished - Mar 1994

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Vinblastine
Granulocyte Colony-Stimulating Factor
Methotrexate
Doxorubicin
Cisplatin
Carcinoma
Leukopenia
Neutropenia
Fever
Radiotherapy
Survival Rate
Confidence Intervals
Drug Therapy
Survival
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

@article{9f640415b55c448985a6dc56792a70bd,
title = "Escalated dosages of methotrexate, vinblastine, doxorubicin, and cisplatin plus recombinant human granulocyte colony-stimulating factor in advanced urothelial carcinoma: An eastern cooperative oncology group trial",
abstract = "Purpose: This multicenter cooperative group phase I/ II trial evaluated the toxicity and efficacy of escalated dosages of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) with recombinant human granulocyte colony-stimulating factor (rhG-CSF) in patients with advanced urothelial carcinoma. Patients and Methods: From November 1990 through October 1991, 35 patients with advanced urothelial cancer previously untreated with chemotherapy were treated with escalated dosages of M-VAC (M-VACII). In patients with prior pelvic radiotherapy, standard M-VAC (M-VACI) was administered plus rhG-CSF. For other patients, M-VACII dosages were methotrexate 40 mg/m2 (days 1, 15, and 22), vinblastine 4 mg/m2 (days 2, 15, and 22), doxorubicin 40 mg/m2 (day 2), and cisplatin 100 mg/m2 (day 2). In addition, rhG-CSF was administered at a dosage of 300 μg subcutaneously on days 4 to 11. Cycles were repeated every 4 weeks. For patients who tolerated the first course of therapy, subsequent escalation by 25{\%} of all drugs was performed. Results: Six complete responses and 15 partial responses were observed (60{\%}; 95{\%} confidence interval, 42{\%} to 76{\%}). The median duration of response was 4.6 months, and the median survival time was 9.4 months (range, 0.5 to 23.5+). Twenty-eight of 35 patients experienced grade 3 or 4 leukopenia, including 14 patients who developed fever associated with neutropenia. Eight (23{\%}) early deaths were observed. Conclusion: This regimen (M-VACII) with escalated dosages of M-VAC was associated with significant toxicity and had no apparent benefit over M-VAC1 therapy with regard to complete response rate or survival. Further evaluation of the dose-intensity of the components of this regimen in this disease is likely to be of limited benefit to patients.",
author = "Patrick Loehrer and Paul Elson and Robert Dreicer and Richard Hahn and Nichols, {Craig R.} and Richard Williams and Lawrence Einhorn",
year = "1994",
month = "3",
language = "English",
volume = "12",
pages = "483--488",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "3",

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TY - JOUR

T1 - Escalated dosages of methotrexate, vinblastine, doxorubicin, and cisplatin plus recombinant human granulocyte colony-stimulating factor in advanced urothelial carcinoma

T2 - An eastern cooperative oncology group trial

AU - Loehrer, Patrick

AU - Elson, Paul

AU - Dreicer, Robert

AU - Hahn, Richard

AU - Nichols, Craig R.

AU - Williams, Richard

AU - Einhorn, Lawrence

PY - 1994/3

Y1 - 1994/3

N2 - Purpose: This multicenter cooperative group phase I/ II trial evaluated the toxicity and efficacy of escalated dosages of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) with recombinant human granulocyte colony-stimulating factor (rhG-CSF) in patients with advanced urothelial carcinoma. Patients and Methods: From November 1990 through October 1991, 35 patients with advanced urothelial cancer previously untreated with chemotherapy were treated with escalated dosages of M-VAC (M-VACII). In patients with prior pelvic radiotherapy, standard M-VAC (M-VACI) was administered plus rhG-CSF. For other patients, M-VACII dosages were methotrexate 40 mg/m2 (days 1, 15, and 22), vinblastine 4 mg/m2 (days 2, 15, and 22), doxorubicin 40 mg/m2 (day 2), and cisplatin 100 mg/m2 (day 2). In addition, rhG-CSF was administered at a dosage of 300 μg subcutaneously on days 4 to 11. Cycles were repeated every 4 weeks. For patients who tolerated the first course of therapy, subsequent escalation by 25% of all drugs was performed. Results: Six complete responses and 15 partial responses were observed (60%; 95% confidence interval, 42% to 76%). The median duration of response was 4.6 months, and the median survival time was 9.4 months (range, 0.5 to 23.5+). Twenty-eight of 35 patients experienced grade 3 or 4 leukopenia, including 14 patients who developed fever associated with neutropenia. Eight (23%) early deaths were observed. Conclusion: This regimen (M-VACII) with escalated dosages of M-VAC was associated with significant toxicity and had no apparent benefit over M-VAC1 therapy with regard to complete response rate or survival. Further evaluation of the dose-intensity of the components of this regimen in this disease is likely to be of limited benefit to patients.

AB - Purpose: This multicenter cooperative group phase I/ II trial evaluated the toxicity and efficacy of escalated dosages of methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) with recombinant human granulocyte colony-stimulating factor (rhG-CSF) in patients with advanced urothelial carcinoma. Patients and Methods: From November 1990 through October 1991, 35 patients with advanced urothelial cancer previously untreated with chemotherapy were treated with escalated dosages of M-VAC (M-VACII). In patients with prior pelvic radiotherapy, standard M-VAC (M-VACI) was administered plus rhG-CSF. For other patients, M-VACII dosages were methotrexate 40 mg/m2 (days 1, 15, and 22), vinblastine 4 mg/m2 (days 2, 15, and 22), doxorubicin 40 mg/m2 (day 2), and cisplatin 100 mg/m2 (day 2). In addition, rhG-CSF was administered at a dosage of 300 μg subcutaneously on days 4 to 11. Cycles were repeated every 4 weeks. For patients who tolerated the first course of therapy, subsequent escalation by 25% of all drugs was performed. Results: Six complete responses and 15 partial responses were observed (60%; 95% confidence interval, 42% to 76%). The median duration of response was 4.6 months, and the median survival time was 9.4 months (range, 0.5 to 23.5+). Twenty-eight of 35 patients experienced grade 3 or 4 leukopenia, including 14 patients who developed fever associated with neutropenia. Eight (23%) early deaths were observed. Conclusion: This regimen (M-VACII) with escalated dosages of M-VAC was associated with significant toxicity and had no apparent benefit over M-VAC1 therapy with regard to complete response rate or survival. Further evaluation of the dose-intensity of the components of this regimen in this disease is likely to be of limited benefit to patients.

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