Will doublet chemotherapy and radiation improve outcome as compared to standard treatment in carcinoma cervix IIIB? Long term results of a prospective randomized phase III trial

Abstract

Background: Despite the use of concurrent chemoradiotherapy (C-CRT) with cisplatin in locally advanced carcinoma cervix, many patients continue to fail in the pelvis (20-25%) and at distant sites (10-20%). These relapses are more pronounced in stage IIIB patients. Cochrane Meta-analysis has also shown decreasing relative effect of C-CRT on survival with increasing tumor stage (3% in stage III). To improve upon these results various strategies have been studied, one of which is use of combination chemotherapy, which was tested in the present analysis. Methods: From 1/6/10 to 31/5/12, 70 Women with newly diagnosed, histopathologi-cally proven squamous cell carcinoma cervix with FIGO stage IIIB were randomized to two arms, cisplatin 40mg/m2/week for 5 weeks was given in cisplatin (C) arm while cisplatin 30mg/m2/week and paclitaxel 50mg/m2/week for 5 weeks were given in cisplatin and paclitaxel (CP) arm along with conformal radiotherapy (46Gy/23#/4.5weeks) followed by high dose rate brachytherapy (8Gy x 3#). Acute toxicities were monitored by RTOG criteria. Overall survival (OS) and Disease-free survival (DFS) were compared at median follow up. Results: Patient and disease characteristics were comparable in both the groups. Median age was 52 years in both groups; median duration of treatment was 8weeks with a median follow up of 45 months in both the groups. Acute toxicities, evaluated weekly during treatment and at first follow up, were comparable for hematological and cutaneous toxicities however grade III & IV Gastrointestinal toxicities were significantly more in CP arm 18 Vs6 (p =0.002). No statistically significant difference was found in DFS (52.9% Vs 47.2%) and OS (58.8% Vs 50%) between CP and C arm at median follow up. Conclusions: Increase in toxicity with failure to improve outcome by addition of pacli-taxel to Cisplatin in patients already receiving maximal dose of radiation point towards limits of these schedules. To further improve outcome with fewer side effects newer areas including molecular targets and immunotherapy needs to be evaluated.