Phase III Comparative Study of Vinorelbine Combined With Doxorubicin Versus Doxorubicin Alone in Disseminated Metastatic/Recurrent Breast Cancer: National Cancer Institute of Canada Clinical Trials Group Study MA8

• Published in: Journal of clinical oncology Vol. 18; no. 12; pp. 2385 - 2394
• Main Authors: NORRIS, B, PRITCHARD, K. I, LATREILLE, J, RUDINSKAS, L, LOFTERS, W, TRUDEAU, M, OSOBA, D, RODGERS, A, JAMES, K, MYLES, J, BENNETT, K, MARLIN, S, SKILLINGS, J, FINDLAY, B, VANDENBERG, T, GOSS, P
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 01-06-2000; Lippincott Williams & Wilkins
• Subjects: Adult; Aged; Antineoplastic agents; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Chemotherapy; Disease Progression; Doxorubicin - administration & dosage; Doxorubicin - adverse effects; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Quality of Life; Survival Analysis; Treatment Outcome; Vinblastine - administration & dosage; Vinblastine - adverse effects; Vinblastine - analogs & derivatives; Human; Antineoplastic agent; Phase III trial; Drug combination; Relapse; Carcinoma; Malignant tumor; Doxorubicin; Mammary gland diseases; Alkaloid; Chemotherapy; Randomization; Treatment; Adult; Anthracyclins; Metastatic; Mammary gland; Comparative study; Vinorelbine
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2000.18.12.2385

This phase III study was performed to determine the superiority of doxorubicin (DOX) and vinorelbine (VNB) (arm 1) versus DOX alone (arm 2) in metastatic breast cancer (MBC) for overall survival (OS), time to treatment failure (TTF), toxicity, and quality of life (QOL).
Three hundred three patients were randomized to DOX 50 mg/m(2) intravenously (IV) on day 1 and VNB 25 mg/m(2) IV on days 1 and 8 (arm 1) or DOX 70 mg/m(2) IV on day 1 (arm 2). Both regimens were given every 3 weeks until a cumulative DOX dose of 450 mg/m(2). After 16 of the first 65 randomized patients experienced febrile neutropenia (FN), the doses were reduced to DOX 40 mg/m(2) on day 1 and VNB 20 mg/m(2) on days 1 and 8 versus DOX 60 mg/m(2) on day 1. Eligible patients were vinca alkaloid and anthracycline naive. Chemotherapy was first-line or second-line for MBC.
Three patients were ineligible. Thus, 300 patients were assessable for toxicity and to determine time to disease progression (TTP), TTF, and OS. Two hundred eighty-nine patients were assessable for response, and 99 responders were assessable for response duration (RD). The response rates, QOL, and median RD, TTP, and TTF were not significantly different between the arms. Median OS was 13.8 months for arm 1 versus 14.4 months for arm 2 (P =.4). Grade 3 or 4 granulocytopenia was equivalent in both arms but more grade 3/4 neurotoxicity, mild venous toxicity, and FN were seen on arm 1.
The survival with DOX and VNB is not superior to DOX alone in MBC.