INDUCTION CHEMOTHERAPY FOLLOWED BY CONCOMITANT CHEMORADIOTHERAPY FOR ADVANCED HEAD AND NECK-CANCER - IMPACT ON THE NATURAL-HISTORY OF THE DISEASE

Purpose: To determine survival rates and the pattern of failure in hea d and neck cancer patients treated with induction chemotherapy, limite d surgery and concomitant chemoradiotherapy. Patients and Methods: Thr ee cycles of induction chemotherapy with cisplatin, fluorouracil (5-FU ), leucovorin, and interferon alfa-2b (PFL-IFN) were followed by optio nal surgery, and seven or eight cycles of 5-FU, hydroxyurea, and concu rrent radiation for 5 days (FHX) for a total radiation dose of 65 to 7 5 Gy. Surgical resection was performed with the intent to spare organ function. Results: Seventy-one patients were treated at three institut ions, Sixty-five patients (91%) had stage IV disease with N2/3 in 46. Thirty-three patients (51%; 95% confidence interval, 39% to 63%) achie ved a clinical complete response (CR) to PFL-IFN. Local therapy consis ted of surgery in 37 and/or FHX in 55 patients. With a median follow-u p duration of 37 months, there have been 20 recurrences (15 local, fou r distant, and one both local and distant), and 29 deaths, 15 in patie nts with disease progression and 14 not directly related to the primar y tumor, Four patients have developed second malignancies. At 3 years, 69% (+/- 6%) are progression-free and the overall survival rate is 60 % (+/- 6%). Toxicity of PFL-IFN included severe or life-threatening mu cositis (54%) and myelosuppression (60%), Five patients died of toxici ty, During FHX, 70% of patients had grade 3 or 4 mucositis. Conclusion : PFL-IFN is highly active, producing clinical CRs in 51% of patients, and, when followed by FHX, resulting in high local and distant contro l and overall survival rates, Second malignancies and intercurrent med ical disease emerge as major risks to long-term survival. In view of t he high toxicity and long treatment duration, further modifications of this approach are required. J Clin Oncol 13:816-883. (C) 1995 by Amer ican Society of Clinical Oncology.