Role of multimodal treatment in oropharynx, larynx, and hypopharynx cancer.

Due to recent advances in radiation fractionation, radiochemotherapy, and conservative surgical techniques, the concept of multimodal therapy in head and neck cancer is currently changing. The recently published RTOG Phase III trial 9003, with 1,113 patients accrued, showed that hyperfractionation and accelerated fractionation with concomitant boost are more efficacious than standard fractionation for locally-advanced head and neck cancer. Acute, but not late, toxicity was also increased. Three meta-analyses have suggested that the impact of chemotherapy in head and neck cancer is small but is highly associated with the timing of therapy. Concomitant administration of radiation therapy and chemotherapy led to an absolute benefit in 5-year survival of about 10%. This finding has been further supported by recently published randomized prospective trials comparing concomitant radiochemotherapy with radiotherapy alone in advanced head and neck cancer. There is now clear evidence that radiochemotherapy provides a substantial and statistically significant improvement in survival and local-regional control, as compared to radiotherapy alone. Radiochemotherapy should be considered an accepted standard of care in cancers of the oropharynx, particularly for patients with locally-advanced disease who have a good performance status. Two randomized studies conducted by the Department of Veterans' Affairs and the EORTC, with a total of 534 patients accrued, showed that induction chemotherapy followed by radiotherapy of responders yields survival rates equal to those of total laryngectomy with postoperative radiotherapy. After 4 years, one-half to two-thirds of survivors of the chemotherapy arm retained a functional larynx. Larynx preservation using induction chemotherapy can now be regarded as feasible but still investigational. Current phase II studies show excellent larynx preservation rates using a primary concomitant radiochemotherapy with an altered fractionation regimen. More clinical and laboratory research is required to further evaluate the different treatment options of the multimodality concept, and to develop prognostic models that will allow individualization of the therapy.