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.
OBJECTIVE
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.


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.


RESULTS
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.


CONCLUSIONS
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.
Bamias
A
A
Department of Clinical Therapeutics Urology, Hygiene and Epidemiology, University of Athens School of Medicine, Athens, Greece. abamias@med.uoa.gr
Aravantinos
G
G
Deliveliotis
C
C
Bafaloukos
D
D
Kalofonos
C
C
Xiros
N
N
Zervas
A
A
Mitropoulos
D
D
Samantas
E
E
Pectasides
D
D
Papakostas
P
P
Gika
D
D
Kourousis
C
C
Koutras
A
A
Papadimitriou
C
C
Bamias
C
C
Kosmidis
P
P
Dimopoulos
M A
MA
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D018450:Disease Progression; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D011379:Prognosis; D043823:Taxoids / Q000008:administration & dosage; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014747:Vinblastine / Q000008:administration & dosage
D043823:Taxoids; D016179:Granulocyte Colony-Stimulating Factor; D000077143:Docetaxel; D014747:Vinblastine; D004317:Doxorubicin; D002945:Cisplatin; D008727:Methotrexate