Preoperative combined chemotherapy and radiation therapy plus radical surgery in advanced head and neck cancer. Five-year results with impressive complete response rates and high survival.

Abstract

Radiation therapy combined with cisplatin as a chemoradiation sensitizer (CT/RT) has been reported to enhance tumor response in squamous cell carcinoma of the head and neck. In the present study, CT/RT was used preoperatively in advanced Stage III and IV head and neck cancer. Fifty-three patients were entered prospectively into a Phase II study. Treatment consisted of 4500 cGy of radiation therapy in 5 weeks combined with cisplatin 20 mg/m2 for 4 days during weeks 1 and 4 of radiation therapy. This was followed 4 to 8 weeks later by curative surgery. Pretherapy dental care; long-term nutritional support; individualized skin, mouth, and wound care; and continuous interdisciplinary communication were integral parts of this regimen. In four patients, CT/RT toxicity was seen (8%); three episodes of skin reaction or stomatitis and three episodes of leukopenia (less than 2500/microliters), causing a delay in CT/RT treatment in one patient. Three patients died of other causes during the preoperative interval, without clinical evidence of toxicity. Fifty patients (94%) had a complete (CR) or partial response (PR) to CT/RT. Clinical CR was seen in 38 of 51 (75%) primary tumors and 21 of 27 (78%) cervical nodes. Forty-one patients (77%) underwent curative surgery. In 27 of 32 (84%) resected CR primary tumors and 16 of 18 (89%) CR metastatic nodes, the surgical specimen was microscopically free of tumor. Postoperative morbidity was 32%. Five patients (12%) required additional surgery for their complications. Perioperative mortality was 5%. Five patients had tumor recurrence: three postoperatively after clinical PR to CT/RT and two in clinical CR patients who refused further treatment after CT/RT, then had a recurrence and were salvaged surgically. No patient with a CR in both the tumor and nodes who underwent surgery had a tumor recurrence. With a follow-up of 8 years (median, 40 months), the median survival for all patients was 45 months. The 5-year actuarial survival rate was 43% for all patients and 55% for patients who had CT/RT and surgery. This multimodality treatment of advanced head and neck cancer has low toxicity and impressive survival. It renders a significant number of patients tumor-free before surgery. These patients may be candidates for additional study triaging additional CT/RT for complete CR only and surgery for PR and biopsy-proved residual disease.