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.

Abstract

PURPOSE:

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 AND METHODS:

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.

RESULT:

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.

CONCLUSION:

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.

• Authors: A Bamias, G Aravantinos, C Deliveliotis, D Bafaloukos, C Kalofonos, N Xiros, A Zervas, D Mitropoulos, E Samantas, D Pectasides, P Papakostas, D Gika, C Kourousis, A Koutras, C Papadimitriou, C Bamias, P Kosmidis, M A Dimopoulos, Hellenic Cooperative Oncology Group
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 22 Issue 2 Pg. 220-8 (Jan 15 2004) ISSN: 0732-183X [Print] United States
• PMID: 14665607 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Taxoids
• Granulocyte Colony-Stimulating Factor
• Docetaxel
• Vinblastine
• Doxorubicin
• Cisplatin
• Methotrexate

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, therapeutic use)
• Cisplatin (administration & dosage)
• Disease Progression
• Docetaxel
• Doxorubicin (administration & dosage)
• Female
• Granulocyte Colony-Stimulating Factor (administration & dosage)
• Humans
• Male
• Methotrexate (administration & dosage)
• Middle Aged
• Neutropenia (chemically induced)
• Prognosis
• Taxoids (administration & dosage)
• Thrombocytopenia (chemically induced)
• Treatment Outcome
• Urologic Neoplasms (drug therapy, pathology)
• Vinblastine (administration & dosage)