A systematic review of acute and late toxicity of concomitant chemoradiation for cervical cancer

Background and purpose: Concomitant chemoradiation (CRT) for locally advanced cervical cancer has become an established treatment based on randomised trials. Major concerns, however, remain over the acute and late toxicity and hence the generalisability of the conclusions of these studies. Materials and methods: A review of all known randomised trials using the Cochrane Collaboration methodology identified 19 trials (17 published, two unpublished) between 1981 and 2000 including 4580 randomised patients. Data on toxicity were available for 1766 patients. The trials differed in size, design, and accrual period. As a conceptual ranking, six grades of severity were used in all scales; groups 1-4 were combined to allow comparison of CRT and radiotherapy and expressed as an odds ratio. This systematic review examines the toxicity of the meta-analysis, with the cisplatin containing trials discussed separately. Results: Grade 1 and 2 haematological toxicities were higher in the CRT group. Significant differences were seen in grade 3 and 4 haematological and gastrointestinal toxicities where a twofold increase in white cell count [OR 2.15 CI 95% (1.57-2.95) P < 0.001], a threefold increase in platelet toxicity [OR 3.04 CI 95% (1.08-8.51) P = 0.005] and a twofold increase in gastrointestinal toxicity [OR 1.92 CI 95% (1.26-2.92) P < 0.001] were seen. Long-term toxicity was only described in eight trials, seven of which reported no statistical difference. Conclusions: In view of the consistency and extent of the survival benefit for CRT the additional acute toxicity appears to be acceptable. The lack of data on long-term toxicity needs to be addressed. (C) 2003 Elsevier Ireland Ltd. All rights reserved.