Gemcitabine plus cisplatin versus gemcitabine plus carboplatin as first-line chemotherapy in advanced transitional cell carcinoma of the urothelium: results of a randomized phase 2 trial.
OBJECTIVE
This phase 2 randomized study compared the toxicity and assessed the efficacy of gemcitabine-cisplatin (GP) and gemcitabine-carboplatin (GC) in patients with advanced transitional cell carcinoma of the urothelium (TCC), with the main objective to demonstrate a reduction in toxicity of at least 25% in the GC arm.


METHODS
A total of 110 chemonaive patients (55 per arm) with locally advanced or metastatic TCC received gemcitabine 1250 mg/m(2) on days 1 and 8 plus cisplatin 70 mg/m(2) on day 2 (GP) every 3 wk or gemcitabine 1250 mg/m(2) on days 1 and 8 plus carboplatin AUC 5 on day 2 (GC) every 3 wk for a maximum of six cycles.


RESULTS
No differences between arms were noted in the overall toxicity profiles and any parameter of toxicity. The most frequent grade 3-4 hematologic toxicity was neutropenia in 34.6% of patients for GP and 45.4% for GC. The most frequent grade 3-4 nonhematologic toxicity was nausea and vomiting (GP: 9.1%; GC: 3.6%). Grade 1-2 nephrotoxicity occurred in 14 GP-treated patients (26.0%) and 9 GC-treated patients (16.3%). Per an intent-to-treat analysis, overall response, evaluated on 80 patients, was 49.1% for GP (CR: 14.5%; PR: 34.5%) and 40.0% for GC (CR: 1.8%; PR: 38.2%). Median time to progression was 8.3 mo for GP and 7.7 mo for GC. Median survival was 12.8 mo and 9.8 mo for GP and GC, respectively.


CONCLUSIONS
GC has a comparably acceptable toxicity profile compared with that of GP and seems active in patients with TCC.
Dogliotti
Luigi
L
Unit of Medical Oncology, University of Torino, San Luigi Hospital, Orbassano-Torino, Italy. luigi.dogliotti@unito.it
Cartenì
Giacomo
G
Siena
Salvatore
S
Bertetto
Oscar
O
Martoni
Andrea
A
Bono
Aldo
A
Amadori
Dino
D
Onat
Haluk
H
Marini
Luca
L
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D016190:Carboplatin / Q000008:administration & dosage; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012189:Retrospective Studies; D015996:Survival Rate; D013997:Time Factors; D016896:Treatment Outcome; D014421:Turkey / Q000453:epidemiology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D019459:Urothelium / Q000473:pathology*; D000093542:Gemcitabine
D003841:Deoxycytidine; D016190:Carboplatin; D002945:Cisplatin; D000093542:Gemcitabine