Efficacy and tolerability of Paclitaxel-Gemcitabine therapy for urothelial carcinoma in patients who have received prior platinum-based chemotherapy.

Abstract

443 Background: Although platinum-based chemotherapy is the standard regimen as first line chemotherapy for urothelial carcinoma, the optimal second line regimen has not been yet established. The objective of this study was to evaluate the efficacy and safety of combination chemotherapy with paclitaxel (PTX) and gemcitabine (GEM) (PG therapy) for patients who have received prior platinum-based chemotherapy. Methods: We reviewed consecutive patients with locally advanced or metastatic urothelial carcinoma who received PG therapy after platinum-based chemotherapy. Doses and schedule of PG therapy were as follows; PTX, 200mg/m2on day 1, GEM, 1000/m2 on days 1, 8, 15, repeated every 21 days. Imaging studies to assess the efficacy was repeated every 2 cycles of the therapy. Results: We identified 52 eligible patients. Of 52 patients, complete response (CR), partial response (PR), stable disease and progressive disease were observed in 2 (3.8%), 14 (26.9%), 18 (34.6%) and 18 (34.6%), respectively. With the median follow-up period of 9.8(IQR 5.5-16.3) months, the median progression free survival (PFS) after PG therapy was 4.7 months [95% confidence interval (CI), 3.6-5.8] and median overall survival (OS) after PG therapy was 11.6 months (95%CI:8.6-15.3). The sensitivity to PG therapy differed in disease sites, the response rate (CR+PR) of primary site, metastases in lymph nodes, lung, bone and liver was 8.3%, 48.7%, 29.4%, 0% and 33.3%, respectively. The response (CR or PR) to PG therapy [Hazard ratio (HR);0.42, 95% CI 0.18-0.95, p=0.04] and primary site (upper urinary tract) (HR;2.24, 95% CI 1.09-4.62, p=0.03) were associated with longer and shorter PFS, respectively. The response to PG therapy was also identified as a significant independent predictive factor for longer OS (HR;0.31, 95% CI 0.12-0.77, p=0.01). Myelosuppression was the most common adverse event. Only one patient discontinued the treatment due to an adverse event and there were no therapy-related deaths. Conclusions: PG therapy was safe and effective as second line regimen after platinum-based chemotherapy for urothelial carcinoma, especially in primary, lymph node and lung lesions.