Effects of different chemotherapy regimens on survival for advanced cervical cancer: Systematic review and meta-analysis

Background: A large number of trials have assessed various chemotherapy regimens for the treatment of advanced cervical cancer, but there is uncertainty about the magnitude of survival benefits. Methods: We searched (last update January 2006) for trials in women with locally advanced or disseminated cervical cancer that compared neo-adjuvant or concurrent chemotherapy plus radiotherapy versus radiotherapy atone; or different chemotherapy regimens among themselves (with or without background radiotherapy in both arms). Sixty-five trials were identified with survival data on 11,180 women. Resutts for survival were combined with fixed and random effects models and between-study heterogeneity was estimated. Separate results were obtained for different regimens, cycle length, and type of chemotherapy (neo-adjuvant, concurrent, without radiotherapy). Results: Twenty two comparisons had survival. data on 3837 women randomized to receive chemotherapy plus radiotherapy versus radiotherapy atone; the summary relative hazard for mortality was 0.95, 95% CI, 0.83-1.08. Modest between-study heterogeneity (I-2 = 38%) seemed to be due to contradictory results in early trials; trials published in the last decade had a summary relative hazard 0.89 (95% CI, 0.78-1.02) and no between-study heterogeneity (I-2 = 0%).Results were similar for neo-adjuvant chemotherapy and for concurrent chemo-radiotherapy. Cisplatin or cisplatin-based combinations had no significant benefit overall, but a potential benefit was seen with short-length cycles (<= 14 days) and a marginally significant harm with longer-length cycles (summary relative hazards 0.80, 95% CI, 0.66-0.99 and 1.18, 95% CI, 1.02-1.38, respectively). The summary relative hazard was 1.02, (95% CI, 0.84-1.24) for trials using neo-adjuvant chemotherapy and 0.85 (95% CI, 0.73-1.00) for trials using concurrent chemotherapy. Conclusions: Evidence on chemotherapy in women with advanced cervical cancer is not encouraging for major survival benefits. However, small benefits have been observed in some trials, especially with short-length cycles of cisplatin-based regimens and concurrent chemotherapy and radiotherapy. (c) 2006 Published by Elsevier Ltd.