Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: three meta-analyses of updated individual data

Background Despite more than 70 randomised trials, the effect of chemothera py on non-metastatic head and neck squamous-cell carcinoma remains uncertai n. We did three meta-analyses of the impact of survival on chemotherapy add ed to locoregional treatment. Methods We updated data on all patients in randomised trials between 1965 a nd 1993, We included patients with carcinoma of the oropharynx, oral cavity , larynx, or hypopharynx. Findings The main meta-analysis of 63 trials (10 741 patients) of locoregio nal treatment with or without chemotherapy yielded a pooled hazard ratio of death of 0.90 (95% CI 0.85-0.94, p<0.0001), corresponding to an absolute s urvival benefit of 4% at 2 and 5 years in favour of chemotherapy. There was no significant benefit associated with adjuvant or neoadjuvant chemotherap y. Chemotherapy given concomitantly to radiotherapy gave significant benefi ts, but heterogeneity of the results prohibits firm conclusions. Meta-analy sis of six trials (861 patients) comparing neoadjuvant chemotherapy plus ra diotherapy with concomitant or alternating radiochemotherapy yielded a haza rd ratio of 0.91 (0.79-1.06) in favour of concomitant or alternating radioc hemotherapy, Three larynx-preservation trials (602 patients) compared radic al surgery plus radiotherapy with neoadjuvant chemotherapy plus radiotherap y in responders or radical surgery and radiotherapy in non-responders. The hazard ratio of death in the chemotherapy arm as compared with the control arm was 1.19 (0.97-1.46). Interpretation Because the main meta-analysis showed only a small significa nt survival benefit in favour of chemotherapy, the routine use of chemother apy is debatable. For larynx preservation, the non-significant negative eff ect of chemotherapy in the organ-preservation strategy indicates that this procedure must remain investigational.