Intensification regimen 2 for advanced head and neck squamous cell carcinomas

Objective: To determine the feasibility, toxicity, and compliance of an int ense treatment regimen for patients with advanced, previously untreated, re sectable head and neck squamous cell carcinomas. Design: Prospective, nonrandomized, controlled (phase 1 or 2) clinical tria l; median time at risk, 25 months (range, 7 days to 36 months). Setting: Arthur G. James Cancer Hospital and Richard J. Solove Research Ins titute, The Ohio State University, Columbus. Patients: Forty-three patients (median age, 59 years; range, 32-76 years) w ith resectable, previously untreated stage III or IV squamous cell carcinom as of the oral cavity, oropharynx, or hypopharynx or stage II squamous cell carcinomas of the hypopharynx (referred sample of patients). Interventions: Days 1 to 4, perioperative, slightly accelerated, hyperfract ionated radiotherapy (9.1 Gy) to off cord fields; days 1 to 3, cisplatin, 3 0 mg/m(2) per day; day 4, surgical resection and intraoperative radiotherap y boost (7.5 Gy); days 45 to 52, postoperative radiotherapy (40 Gy to the p rimary site and upper neck and 45 Gy to the supraclavicular areas); days 24 , 45, and 66, paclitaxel, 135 mg/m(2) per 24 hours, with routine granulocyt e colony-stimulating factor support; and days 25 and 46, cisplatin, 100 mg/ m(2). Main Outcome Measures: Toxicity, compliance, local control, and distant met astatic rates. Results: Patient compliance was 91% (39 of 43 patients),but protocol compli ance was only 58% (25 of 43 patients), reflecting increased toxicity of the systemic regimen (2 [5%] of the 43 patients experienced grade 5 hematologi c toxicity due to the regimen; 16 [37%], grade 4; and 10 [23%],grade 3). Lo cal-regional control was 92% (23 of: 25 patients), and the distant metastat ic rate was 8% (2 of:25) in patients completing treatment per protocol. One patient had surgical salvage of a second primary tumor. Conclusions: Local control and patient compliance were encouraging, but sys temic toxicity was unacceptable. Thus, the paclitaxel was changed to a week ly regimen.