A Cochrane review included 25 studies with a total of 3 752 subjects; 19 studies (n=2 728) compared concurrent chemoradiotherapy with radiotherapy alone and 6 studies (n=1 024) compared concurrent with sequential chemoradiotherapy.
Addition of concurrent chemotherapy to radical radiotherapy reduced the overall risk of death (HR 0.71, 95% CI 0.64 to 0.80; n=1 607) and increased overall progression-free survival at any site i.e. distant or locoregional, (HR 0.69, 95% CI 0.58 to 0.81; n=1 145). The incidence of acute oesophagitis, neutropenia and anaemia were significantly increased by concurrent chemoradiotherapy.
Concurrent chemoradiotherapy reduced the risk of death compared to sequential chemoradiotherapy (HR 0.74; 95% CI 0.62 to 0.89; n=702). This represented a 10% absolute survival benefit at 2 years. Only two studies reported progression-free survival, which was not significantly different between the two groups. More treatment-related deaths (4% vs 2%) were reported in the concurrent arm without statistical significance (RR 2.02, 95% CI 0.90 to 4.52; n=950). There was increased severe oesophagitis with concurrent treatment (RR 4.96, 95% CI 2.17 to 11.37, statistical heterogeneity I2 66%; n=947).
Comment: The quality of evidence is downgraded by study quality (inadequate or unclear allocation concealment).