A Cochrane review included 18 studies with a total of 3452 subjects, who were randomised between radiotherapy (with or without surgery) versus concomitant chemoradiotherapy (with or without surgery). Overall 5-year survival was higher with chemoradiotherapy compared with the same radiotherapy (hazard ratio HR 0.81, 95 % CI 0.71 to 0.91; 13 trials, n=3104). A clear survival benefit was seen for the 2 further trials in which chemotherapy was administered after chemoradiotherapy compared with radiotherapy only (HR 0.46, 95 % CI 0.32 to 0.66, n=348). There was a survival benefit for both the group of trials that used platinum-based (HR 0.83, 0.71 to 0.97, n=1670) and non-platinum based (HR 0.77, 0.63 to 0.94, n=1458) chemoradiotherapy vs radiotherapy. Chemoradiotherapy also reduced local and distant recurrence and progression and improved disease-free survival. There was a suggestion of a difference in the size of the survival benefit with tumour stage, but not across other patient subgroups. Acute haematological and gastro-intestinal toxicity were increased with chemoradiotherapy, but data were too sparse for an analysis of late toxicity.
A Cochrane review included 2 studies with a total of 978 subjects. One industry-funded trial involving 515 women compared CCRT (cisplatin) versus CCRT (cisplatin and gemcitabine) plus ACT (two additional cycles). This trial reported significant improvement in progression-free survival (PFS) and overall survival (OS) in women who were given CCRT plus ACT compared with those treated with CCRT alone: Three-year PFS was 74.4% versus 65.0% (hazard ratio (HR) 0.68, 95% CI 0.49 to 0.95), and three-year overall survival was 80% versus 69% (HR 0.68, 95% CI 0.49 to 0.95, P value 0.022). However, as the CCRT chemotherapy differed between the two arms, there was a high risk of bias. The second trial was a four-arm study with extracted data on 463 women in two study arms receiving CCRT (intravenous mitomycin C and oral 5-fluorouracil (5-FU)) or CCRT plus ACT (oral 5-FU for three cycles). The HR for overall sruvival in women who received ACT after CCRT compared with CCRT alone was 1.309 (95% CI 0.795 to 2.157), and the HR for disease-free survival (DFS) was 1.125 (95% CI 0.799 to 1.586). Haematological adverse events were more common in the ACT arms of both trials. Quality of life (QoL) was not reported in either trial.