Meta-analysis of randomized trials comparing cisplatin versus carboplatin-based regimens for the first-line therapy of metastatic transitional cell carcinoma of the urothelium (TCCU).

247 Background: Cisplatin-based chemotherapy is the first-line treatment standard for metastatic TCCU, although carboplatin is substituted for cisplatin-ineligibility, tolerability, and ease of administration. Since definitive data comparing cisplatin- versus carboplatin-based chemotherapy are lacking, a meta-analysis of published randomized trials was performed. METHODS PubMed was searched for articles published in the English language from 1966 until 2010 and abstracts presented at the American Society of Clinical Oncology Annual Meeting between 2000 and 2010 were searched to identify relevant trials. Eligible studies included prospective randomized trials evaluating cisplatin- versus carboplatin-based regimens in cisplatin-eligible patients with metastatic TCCU. Individual patient data were not available and progression and survival data were inconsistently reported. Therefore, the analysis focused on overall (OR) and complete response (CR). The Mantel-Haenszel method was used for combining trials and calculating pooled risk ratios (RR). RESULTS A total of 286 patients with metastatic TCCU from 4 randomized trials (3 phase II and 1 phase III trial) were included. Chemotherapy regimens included MVEC (methotrexate, vinblastine, epirubicin, cisplatin) vs. MVECa (methotrexate, vinblastine, epirubicin, carboplatin), MVAC (methotrexate, vinblastine, doxorubicin, cisplatin) vs. MCAVI (methotrexate, carboplatin, vinblastine), MVAC vs. paclitaxel plus carboplatin, and gemcitabine plus cisplatin vs. gemcitabine plus carboplatin. Cisplatin-based chemotherapy was associated with a significant improvement in the likelihood of CR (RR=3.973 [95%CI: 1.562 - 10.110], p =0.004) and OR (RR=1.336 [95%CI: 1.043 - 1.712], p=0.025). CONCLUSIONS Cisplatin-based as compared with carboplatin-based combination chemotherapy significantly increases the likelihoods of both OR and CR, in patients with metastatic TCCU. In the absence of definitive phase 3 trials, these results support cisplatin-based regimens as the preferred first-line treatment for cisplatin-eligible patients with metastatic TCCU. No significant financial relationships to disclose.