Larynx preservation trials: a critical appraisal.

Controlled trials testing the concept of laryngeal preservation for patients with locally advanced stage III and IV cancers of the larynx or hypopharynx were initiated in the mid-1980s. Three randomized trials, evaluating the same cisplatin plus 5-fluorouracil induction chemotherapy regimen and conventional radiotherapy compared with surgery and radiotherapy, have been completed, and the results of two are published. In addition, a meta-analysis of these three trials was completed. The studies are critically reviewed. Conclusions from these trials are that the induction approach is feasible; local and regional control are not improved, whereas distant metastases are delayed; there is no evidence of a difference in overall survival; and of the patients alive at 3 and 5 years, a functional larynx can be preserved in 67% and 58%; there are not enough data to know if there are differences in outcome by subsite. Several unanswered questions are being addressed in phase III trials. These include defining the precise contribution of chemotherapy by comparing induction chemotherapy and radiotherapy to treatment with radiotherapy alone; determining if elective neck dissection for patients with N2N3 neck disease would improve survival; and determining whether local control can be improved by using concomitant or alternating chemotherapy and radiotherapy.