Docetaxel and Cisplatin With Granulocyte Colony-Stimulating Factor (G-CSF) Versus MVAC With G-CSF in Advanced Urothelial Carcinoma: A Multicenter, Randomized, Phase III Study From the Hellenic Cooperative Oncology Group

• Published in: Journal of clinical oncology Vol. 22; no. 2; pp. 220 - 228
• Main Authors: BAMIAS, A, ARAVANTINOS, G, PAPAKASTAS, P, GIKA, D, KOUROUSIS, C, KOUTRAS, A, PAPADIMITRIOU, C, BAMIAS, C, KOSMIDIS, P, DIMOPOULOS, M. A, DELIVELIOTIS, C, BAFALOUKOS, D, KALOFONOS, C, XIROS, N, ZERVAS, A, MITROPOULOS, D, SAMANTAS, E, PECTASIDES, D
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 15.01.2004; Lippincott Williams & Wilkins
• Subjects: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Cisplatin - administration & dosage; Disease Progression; Doxorubicin - administration & dosage; Female; Granulocyte Colony-Stimulating Factor - administration & dosage; Humans; Male; Medical sciences; Methotrexate - administration & dosage; Middle Aged; Neutropenia - chemically induced; Prognosis; Taxoids - administration & dosage; Thrombocytopenia - chemically induced; Treatment Outcome; Tumors; Urologic Neoplasms - drug therapy; Urologic Neoplasms - pathology; Vinblastine - administration & dosage; Antineoplastic agent; Phase III trial; Multicenter study; Docetaxel; Cisplatin; Alkylating agent; Granulocyte colony stimulating factor; Randomization; Cancerology; Taxane derivatives; Advanced stage; Comparative study; Platinum II Complexes
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2004.02.152

The combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) represents the standard regimen for inoperable or metastatic urothelial cancer, but its toxicity is significant. We previously reported a 52% response rate (RR) using a docetaxel and cisplatin (DC) combination. The toxicity of this regimen compared favorably with that reported for MVAC. We thus designed a randomized phase III trial to compare DC with MVAC. Patients with inoperable or metastatic urothelial carcinoma; adequate bone marrow, renal, liver, and cardiac function; and Eastern Cooperative Oncology Group performance status < or = 2 were randomly assigned to receive MVAC at standard doses or docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) every 3 weeks. All patients received prophylactic granulocyte colony-stimulating factor (G-CSF) support. Two hundred twenty patients were randomly assigned (MVAC, 109 patients; DC, 111 patients). Treatment with MVAC resulted in superior RR (54.2% v 37.4%; P =.017), median time to progression (TTP; 9.4 v 6.1 months; P =.003) and median survival (14.2 v 9.3 months; P =.026). After adjusting for prognostic factors, difference in TTP remained significant (hazard ratio [HR], 1.61; P =.005), whereas survival difference was nonsignificant at the 5% level (HR, 1.31; P =.089). MVAC caused more frequent grade 3 or 4 neutropenia (35.4% v 19.2%; P =.006), thrombocytopenia (5.7% v 0.9%; P =.046), and neutropenic sepsis (11.6% v 3.8%; P =.001). Toxicity of MVAC was considerably lower than that previously reported for MVAC administered without G-CSF. MVAC is more effective than DC in advanced urothelial cancer. G-CSF-supported MVAC is well tolerated and could be used instead of classic MVAC as first-line treatment in advanced urothelial carcinoma.