Long-term follow-up of a phase III intergroup study of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: A cooperative group study

Scott B. Saxman, Kathleen J. Propert, Lawrence Einhorn, E. David Crawford, Ian Tannock, Derek Raghavan, Patrick Loehrer, Donald Trump

Research output: Contribution to journalArticle

440 Citations (Scopus)

Abstract

Purpose: A previously reported randomized intergroup trial demonstrated that combination chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) was superior to single-agent cisplatin in patients with advanced urothelial carcinoma. We conducted a long-term analysis of patients included in the intergroup trial to examine factors associated with long-term survival. Patients and Methods: Two-hundred fifty-five assessable patients with urothelial carcinoma were randomized to receive either single- agent cisplatin (70 mg/m2 on day 1) or combination chemotherapy with methotrexate (30 mg/m2 on days 1, 15, and 22), vinblastine (3 mg/m2 on days 2, 15, and 22), doxorubicin (30 mg/m2 on day 2), and cisplatin (70 mg/m2 on day 2). Courses were repeated every 28 days. The association between patient characteristics and survival was assessed using Cox proportional hazards models. Results: With long-term follow-up evaluation, survival in the M-VAC arm continues to be superior to cisplatin (P = .00015, log-rank test). Predictors of survival include performance status, histology, and the presence of liver or bone metastasis. Only 3.7% of the patients randomized to M-VAC are alive and continuously disease-free at 6 years. Conclusion: Long-term follow-up evaluation of the intergroup trial confirms that M-VAC is superior to single-agent cisplatin in patients with advanced urothelial carcinoma; however, durable progression-free survival is rare. Patients with non-transitional-cell histology, poor performance status, and/or bone or visceral involvement fare poorly and are unlikely to benefit significantly from M-VAC chemotherapy.

Original languageEnglish
Pages (from-to)2564-2569
Number of pages6
JournalJournal of Clinical Oncology
Volume15
Issue number7
StatePublished - Jul 1997

Fingerprint

Vinblastine
Methotrexate
Doxorubicin
Cisplatin
Carcinoma
Survival
Combination Drug Therapy
Histology
Bone and Bones
Proportional Hazards Models
Disease-Free Survival
Neoplasm Metastasis
Drug Therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Long-term follow-up of a phase III intergroup study of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma : A cooperative group study. / Saxman, Scott B.; Propert, Kathleen J.; Einhorn, Lawrence; Crawford, E. David; Tannock, Ian; Raghavan, Derek; Loehrer, Patrick; Trump, Donald.

In: Journal of Clinical Oncology, Vol. 15, No. 7, 07.1997, p. 2564-2569.

Research output: Contribution to journalArticle

@article{f46428fde4aa46b4a954b3162cdf3647,
title = "Long-term follow-up of a phase III intergroup study of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: A cooperative group study",
abstract = "Purpose: A previously reported randomized intergroup trial demonstrated that combination chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) was superior to single-agent cisplatin in patients with advanced urothelial carcinoma. We conducted a long-term analysis of patients included in the intergroup trial to examine factors associated with long-term survival. Patients and Methods: Two-hundred fifty-five assessable patients with urothelial carcinoma were randomized to receive either single- agent cisplatin (70 mg/m2 on day 1) or combination chemotherapy with methotrexate (30 mg/m2 on days 1, 15, and 22), vinblastine (3 mg/m2 on days 2, 15, and 22), doxorubicin (30 mg/m2 on day 2), and cisplatin (70 mg/m2 on day 2). Courses were repeated every 28 days. The association between patient characteristics and survival was assessed using Cox proportional hazards models. Results: With long-term follow-up evaluation, survival in the M-VAC arm continues to be superior to cisplatin (P = .00015, log-rank test). Predictors of survival include performance status, histology, and the presence of liver or bone metastasis. Only 3.7{\%} of the patients randomized to M-VAC are alive and continuously disease-free at 6 years. Conclusion: Long-term follow-up evaluation of the intergroup trial confirms that M-VAC is superior to single-agent cisplatin in patients with advanced urothelial carcinoma; however, durable progression-free survival is rare. Patients with non-transitional-cell histology, poor performance status, and/or bone or visceral involvement fare poorly and are unlikely to benefit significantly from M-VAC chemotherapy.",
author = "Saxman, {Scott B.} and Propert, {Kathleen J.} and Lawrence Einhorn and Crawford, {E. David} and Ian Tannock and Derek Raghavan and Patrick Loehrer and Donald Trump",
year = "1997",
month = "7",
language = "English",
volume = "15",
pages = "2564--2569",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "7",

}

TY - JOUR

T1 - Long-term follow-up of a phase III intergroup study of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma

T2 - A cooperative group study

AU - Saxman, Scott B.

AU - Propert, Kathleen J.

AU - Einhorn, Lawrence

AU - Crawford, E. David

AU - Tannock, Ian

AU - Raghavan, Derek

AU - Loehrer, Patrick

AU - Trump, Donald

PY - 1997/7

Y1 - 1997/7

N2 - Purpose: A previously reported randomized intergroup trial demonstrated that combination chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) was superior to single-agent cisplatin in patients with advanced urothelial carcinoma. We conducted a long-term analysis of patients included in the intergroup trial to examine factors associated with long-term survival. Patients and Methods: Two-hundred fifty-five assessable patients with urothelial carcinoma were randomized to receive either single- agent cisplatin (70 mg/m2 on day 1) or combination chemotherapy with methotrexate (30 mg/m2 on days 1, 15, and 22), vinblastine (3 mg/m2 on days 2, 15, and 22), doxorubicin (30 mg/m2 on day 2), and cisplatin (70 mg/m2 on day 2). Courses were repeated every 28 days. The association between patient characteristics and survival was assessed using Cox proportional hazards models. Results: With long-term follow-up evaluation, survival in the M-VAC arm continues to be superior to cisplatin (P = .00015, log-rank test). Predictors of survival include performance status, histology, and the presence of liver or bone metastasis. Only 3.7% of the patients randomized to M-VAC are alive and continuously disease-free at 6 years. Conclusion: Long-term follow-up evaluation of the intergroup trial confirms that M-VAC is superior to single-agent cisplatin in patients with advanced urothelial carcinoma; however, durable progression-free survival is rare. Patients with non-transitional-cell histology, poor performance status, and/or bone or visceral involvement fare poorly and are unlikely to benefit significantly from M-VAC chemotherapy.

AB - Purpose: A previously reported randomized intergroup trial demonstrated that combination chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) was superior to single-agent cisplatin in patients with advanced urothelial carcinoma. We conducted a long-term analysis of patients included in the intergroup trial to examine factors associated with long-term survival. Patients and Methods: Two-hundred fifty-five assessable patients with urothelial carcinoma were randomized to receive either single- agent cisplatin (70 mg/m2 on day 1) or combination chemotherapy with methotrexate (30 mg/m2 on days 1, 15, and 22), vinblastine (3 mg/m2 on days 2, 15, and 22), doxorubicin (30 mg/m2 on day 2), and cisplatin (70 mg/m2 on day 2). Courses were repeated every 28 days. The association between patient characteristics and survival was assessed using Cox proportional hazards models. Results: With long-term follow-up evaluation, survival in the M-VAC arm continues to be superior to cisplatin (P = .00015, log-rank test). Predictors of survival include performance status, histology, and the presence of liver or bone metastasis. Only 3.7% of the patients randomized to M-VAC are alive and continuously disease-free at 6 years. Conclusion: Long-term follow-up evaluation of the intergroup trial confirms that M-VAC is superior to single-agent cisplatin in patients with advanced urothelial carcinoma; however, durable progression-free survival is rare. Patients with non-transitional-cell histology, poor performance status, and/or bone or visceral involvement fare poorly and are unlikely to benefit significantly from M-VAC chemotherapy.

UR - http://www.scopus.com/inward/record.url?scp=0030794516&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030794516&partnerID=8YFLogxK

M3 - Article

C2 - 9215826

AN - SCOPUS:0030794516

VL - 15

SP - 2564

EP - 2569

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 7

ER -