Concomitant chemotherapy and radiation therapy for cancer of the uterine cervix

• Published in: Cochrane database of systematic reviews 2005-07, Vol.2005 (3), p.CD002225
• Main Authors: Green, J, Kirwan, J, Tierney, J, Vale, C, Symonds, P, Fresco, L, Williams, C, Collingwood, M
• Format: Article
• Language: English
• Subjects: Cancer; CANCER OF THE UTERINE CERVIX; Combined Modality Therapy; Female; Gynaecology; Humans; Randomized Controlled Trials as Topic; Uterine Cervical Neoplasms - drug therapy; Uterine Cervical Neoplasms - radiotherapy
• ISSN: 1469-493X
• DOI: 10.1002/14651858.cd002225.pub2

The National Cancer Institute (USA) alert in February 1999 stated that concomitant chemoradiotherapy should be considered for all patients with cervical cancer, based on evidence from five randomised controlled trials (RCTs). To review all known RCTs comparing concomitant chemotherapy and radiation therapy with radiotherapy for locally advanced cervical cancer. We searched electronic databases, trials registers and reference lists of published trial reports and review articles were also searched. This review includes RCTs in cervical cancer comparing concomitant chemoradiation with radiotherapy in the experimental arm. Trials allowing further adjuvant chemotherapy or hydroxyurea were included. Trials using radiosensitisers or radioprotectors in the experimental arm were excluded. Two authors reviewed trials for inclusion and extracted data. For meta-analyses of time-to-event outcomes (survival, progression-free survival), a hazard ratio (HR) was extracted or estimated from trial reports, where possible. Only overall rates of local and distant recurrence were presented in many reports so only odds ratios (OR) of recurrence rates could be calculated, which takes no account of time to recurrence or censoring. Few trials reported acute toxicity adequately, but where possible ORs were calculated for the main types and severities of acute toxicity. The HRs and ORs for individual trials were combined across all trials, using the fixed effect model. Late toxicity was rarely described in sufficient detail so could only be reviewed qualitatively. The original review was based on nineteen trials (17 published and two unpublished) including 4580 patients. This update includes twenty four trials (21 published, 3 unpublished) and 4921 patients, although due to patient exclusion and differential reporting 61% to 75% were available for the analyses. The review strongly suggests chemoradiation improves overall survival and progression free survival, whether or not platinum was used with absolute benefits of 10% and 13% respectively. There was, however, statistical heterogeneity for these outcomes. There was some evidence that the effect was greater in trials including a high proportion of stage I and II patients. Chemoradiation also showed significant benefit for local recurrence and a suggestion of a benefit for distant recurrence. Acute haematological and gastrointestinal toxicity was significantly greater in the concomitant chemoradiation group. Late effects of treatmen