Randomized Phase III Trial of High–Dose-Intensity Methotrexate, Vinblastine, Doxorubicin, and Cisplatin (MVAC) Chemotherapy and Recombinant Human Granulocyte Colony-Stimulating Factor Versus Classic MVAC in Advanced Urothelial Tract Tumors: European Organization for Research and Treatment of Cancer Protocol No. 30924

• Published in: Journal of clinical oncology Vol. 19; no. 10; pp. 2638 - 2646
• Main Authors: STERNBERG, C. N, DE MULDER, P. H. M, COLLETTE, L, SCHORNAGEL, J. H, THEODORE, C, FOSSA, S. D, VAN OOSTEROM, A. T, WITJES, F, SPINA, M, VAN GROENINGEN, C. J, DE BALINCOURT, C
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 15.05.2001; Lippincott Williams & Wilkins
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Chemotherapy; Cisplatin - administration & dosage; Disease-Free Survival; Doxorubicin - administration & dosage; Drug Administration Schedule; Europe; Female; Filgrastim; Granulocyte Colony-Stimulating Factor - therapeutic use; Humans; Male; Medical sciences; Methotrexate - administration & dosage; Middle Aged; Neoplasm Metastasis; Pharmacology. Drug treatments; Recombinant Proteins; Urinary Bladder Neoplasms - drug therapy; Urinary Bladder Neoplasms - mortality; Vinblastine - administration & dosage; Europe; Antineoplastic agent; Phase III trial; Prognosis; Transitional cell carcinoma; Urinary tract; Doxorubicin; Antifolate; Alkaloid; Granulocyte colony stimulating factor; Advanced stage; Methotrexate; Antimitotic; High dose; Platinum II Complexes; Human; Drug combination; Urinary system disease; Vinblastine; Cytokine; Malignant tumor; Urinary tract disease; Cisplatin; Alkylating agent; Antibiotic; Chemotherapy; Treatment; Antimetabolic; Polypeptide; Therapeutic protocol; Comparative study
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2001.19.10.2638

This randomized trial evaluated antitumor activity of and survival asociated with high-dose-intensity chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) plus granulocyte colony-stimulating factor (HD-MVAC) versus MVAC in patients with advanced transitional-cell carcinoma (TCC). A total of 263 patients with metastatic or advanced TCC who had no prior chemotherapy were randomized to HD-MVAC (2-week cycles) or MVAC (4-week cycles). Using an intent-to-treat analysis, at a median follow-up of 38 months, on the HD-MVAC arm there were 28 complete responses (CRs) (21%) and 55 partial responses (PRs) (41%), for an overall response of 62% (95% confidence interval [CI], 54% to 70%). On the MVAC arm, there were 12 CRs (9%) and 53 PRs (41%), for an overall response of 50% (95% CI, 42% to 59%). The P value for the difference in CR rate was.009; and for the overall response, it was.06. There was no statistically significant difference in survival (P =.122) or time to progression (P =.114). Progression-free survival was significantly better with HD-MVAC (P=.037; hazard ratio.75; 95% CI.58 to.98). The median progression-free survival time was 9.1 months on the HD-MVAC arm versus 8.2 months on the MVAC arm. The 2-year progression-free survival rate was 24.7% for HD-MVAC (95% CI, 17.1% to 32.3%) versus 11.6% for MVAC (95% CI, 5.9% to 17.4%). With HD-MVAC, it was possible to deliver twice the doses of cisplatin and doxorubicin in half the time, with fewer dose delays and less toxicity. Although a 50% difference in median overall survival was not detected, a benefit was observed in progression-free survival, CR rates, and overall response rates with HD-MVAC.