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 and accelerated hyperfractionated radiation has the potential to eradicate 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 patients with advanced squamous cell cancer of the head and neck (stages III and IV), we conducted a multi-institutional study using accelerated hyperfractionated radiation to maximize local and regional tumor control without adding toxicity. Pattents and methods: Preoperative radiation was given in 1.8 Gy fractions for 2 weeks followed by 1.2 Gy bid hyperfractionation to 46.7 Gy. Continous infusion of cisplatin 20 mg/m2 was given on days 1 through 4 and 22 through 25. Patients were initially assessed with panendoscopy and were subsequently reassessed with biopsy of primary site (±nodes). Patients with negative primary site biopsy received additional hyperfractionated radiation to 76 Gy with simultaneous carboplatin 25 mg/m2 bid for 12 consecutive days. Patients with residual disease after 47 Gy had resection of primary site and node dissection. Of 69 patients treated, 56 were T3 and T4, and 46 were N1, N2, and N3; 17 patients (25%) were stage III and 50 (72%) were stage IV; in 2 patients (3%) the stage was unknown. Results: Treatment was well tolerated with no grade IV toxicities, but there were 13 patients with grade III toxicities (mucositis, dysphagia, or hematological 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-four patients underwent curative surgery. Eleven required resection of the primary and 23 required neck dissection only. At 2 years (median follow-up 12 months), 44 of 69 patients (64%) have no evidence of disease, 9 are dead of disease, 9 are dead of other causes, and 6 are alive with disease. Surgical toxicities were minimal and primarily limited to fibrosis in 12 patients, edema in 8 patients, tracheoesophageal fistula in 1 patient, and delayed wound healing in 1 patient. Late toxicities included xerostomia in 22 patients, dysphagia in 17, and speech impairment in 9. Conclusions: Preoperative concurrent radiotherapy and chemotherapy provides a high level of organ preservation and local and regional control because of the high complete response rate at the primary site. A planned neck dissection with minimal morbidity ensures local/regional control, as well as providing definitive staging information. A randomized evaluation is suggested for this program.