Efficacy and safety of dose-dense chemotherapy in urothelial carcinoma

We conducted a meta-analysis to assess the efficacy and safety of dose-dense chemotherapy in the treatment of patients with urothelial carcinoma. A systematic search was conducted in PubMed, Medline, Embase, Web of Science and Cochrane Collaboration's Central register of controlled trials (CENTRAL) for relevant articles. Data was obtained from 10 trials with a total of 1093 patients. The pooled pathologic complete response (pCR) was 27.8% in the ten studies with a full cohort of 684 patients who received dose-dense methotrexate, vinblastine, adriamycin and cisplatin (dd-MVAC). In the controlled trials, although the difference was not significant, the pCR rate in the dd-MVAC group has a trend of increase (odds ratio (OR) 1.52; 95% confidence interval (CI) 0.78-2.98, P = 0.22) compared with classic MVAC group. A significant improvement of overall survival (OS) (hazard ratio (HR) 0.77, 95% CI 0.61-0.97, p = 0.03) was also observed. Hematologic toxicities were the most frequent grade ≥ 3 toxicities including neutropenia/febrile neutropenia (17.5%), anemia (9.4%) and thrombocytopenia (6.1%). Compared with the classic MVAC group, dd-MVAC was associated with significantly decreased risks of all-grade adverse events (AEs) such as anemia (OR 0.457, 95% CI 0.249-0.840, p = 0.012), febrile neutropenia (OR 0.398 95% CI 0.233-0.681, p = 0.001), and neutropenia (OR 0.373, 95% CI 0.201-0.691, p = 0.002). In conclusion, dose-dense chemotherapy was effective and tolerable in patients with urothelial carcinoma, which could be considered as a reasonable therapeutic option.