PREOPERATIVE CISPLATIN AND ACCELERATED HYPERFRACTIONATED RADIATION INDUCES HIGH TUMOR RESPONSE AND CONTROL RATES IN PATIENTS WITH ADVANCED HEAD AND NECK-CANCER

BACKGROUND: Preoperative therapy with concurrent cisplatin infusion an d accelerated hyperfractionated radiation has the potential to eradica te pools of resistant cells with high-growth fraction that accumulate during standard radiation therapy. Based on preliminary data showing a high complete response rate (necessary for organ preservation) in pat ients with advanced squamous cell cancer of the head and neck (stages Ill and IV), we conducted a multi-institutional study using accelerate d hyperfractionated radiation to maximize local and regional tumor con trol without adding toxicity. PATIENTS AND METHODS: Preoperative radia tion was given in 1.8 Gy fractions for 2 weeks followed by 1.2 Gy BID hyperfractionation to 46.7 Gy. Continuous infusion of cisplatin 20 mg/ m(2) was given on days 1 through 4 and 22 through 25. Patients were in itially assessed with panendoscopy and were subsequently reassessed wi th biopsy of primary site(+/- nodes), Patients with negative primary s ite biopsy received additional hyperfractionated radiation to 76 Gy wi th simultaneous carboplatin 25 mg/m(2) BID for 12 consecutive days, Pa tients with residual disease after 47 Gy had resection of primary site and node dissection. Of 69 patients treated, 56 were T3 and T4, and 4 6 were N1, N2, and N3; 17 patients (25%) were stage III and 50 (72%) w ere stage IV; in 2 patients (3%) the stage was unknown. RESULTS: Treat ment was well tolerated with no grade IV toxicities, but there were 13 patients with grade III toxicities (mucositis, dysphagia, or hematolo gical toxicity), Biopsy specimens were taken from 84% of the patients, and 81% of the primary sites showed pathologic complete response and 49% of the lymph nodes showed a pathologic complete response, Thirty-f our patients underwent curative surgery. Eleven required resection of the primary and 23 required neck dissection only. At 2 years (median f ollowup 12 months), 44 of 69 patients (64%) have no evidence of diseas e, 9 are dead of disease, 9 are dead of other causes, and 6 are alive with disease. Surgical toxicities were minimal and primarily limited t o fibrosis in 12 patients, edema in 8 patients, tracheoesophageal fist uta in 1 patient, and delayed wound healing in 1 patient, Late toxicit ies included xerostomia in 22 patients, dysphagia in 17, and speech im pairment in 9. CONCLUSIONS: Preoperative concurrent radiotherapy and c hemotherapy provides a high level of organ preservation and local and regional control because of the high complete response rate at the pri mary site. A planned neck dissection with minimal morbidity ensures lo cal/regional control, as well as providing definitive staging informat ion. A randomized evaluation is suggested for this program.