Adjuvant and adjunctive chemotherapy in the management of squamous cell carcinoma of the head and neck region. A meta-analysis of prospective and randomized trials.

Abstract

PURPOSE Using the technique of meta-analysis, we aim to illustrate the potential benefit, or lack of it, in adding chemotherapy to locoregional definitive treatment in a prospective randomized setting. PATIENTS AND METHODS Mantel-Haenszel summary analyses were used to test 42 prospective and properly randomized trials for statistically significant differences in the proportion with side effects and in the proportion with response to treatment between the experimental treatment arm (including chemotherapy) and control arm (local definitive treatment only) of the study. Summarized estimates of relative risks of side effects and relative proportions of positive responses were obtained using the summarizing options in PROC FREQ in the SAS computer package. In 25 of 42 studies, sufficient survival information was available to estimate the effect of chemotherapy on the rate of dying per person per unit of time. RESULTS Chemotherapy, when added to local definitive treatment, was found to increase toxicity. This increase is statistically significant. The relative proportion of side effects was 2.17, with a 95% confidence interval of 1.84 to 2.56 and P less than .001. Addition of chemotherapy to local treatment has reduced the mortality rate for treated patients by 11% in the total group (all 25 studies), with a 95% confidence interval of 1% to 19%. This reduction means that at the time 50% of patients in the control arm were still alive, 54% of patients who received chemotherapy would be expected to be alive. Concurrent treatment (11 studies) has reduced the mortality rate by 22%, with a 95% confidence interval of 8% to 33%, which means that at the time 50% of patients in the control arm were still alive, 58% of patients who received chemotherapy would be expected to be alive. CONCLUSION Addition of chemotherapy to local definitive treatment has significantly increased the morbidity of treatment as well as the chance of initial tumor response and local control. A statistically significant improvement in survival was found for the simultaneous use of chemotherapy and local definitive treatment.