Objective: To determine the feasibility, toxicity, and compliance of an intense treatment regimen for patients with advanced, previously untreated, resectable head and neck squamous cell carcinomas.
Design: Prospective, nonrandomized, controlled (phase 1 or 2) clinical trial; median time at risk, 25 months (range, 7 days to 36 months).
Setting: Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, Columbus.
Patients: Forty-three patients (median age, 59 years; range, 32-76 years) with resectable, previously untreated stage III or IV squamous cell carcinomas 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, hyperfractionated radiotherapy (9.1 Gy) to off cord fields; days 1 to 3, cisplatin, 30 mg/m2 per day; day 4, surgical resection and intraoperative radiotherapy boost (7.5 Gy); days 45 to 52, postoperative radiotherapy (40 Gy to the primary site and upper neck and 45 Gy to the supraclavicular areas); days 24, 45, and 66, paclitaxel, 135 mg/m2 per 24 hours, with routine granulocyte colony-stimulating factor support; and days 25 and 46, cisplatin, 100 mg/m2.
Main outcome measures: Toxicity, compliance, local control, and distant metastatic rates.
Results: Patient compliance was 91% (39 of 43 patients), but protocol compliance was only 58% (25 of 43 patients), reflecting increased toxicity of the systemic regimen (2 [5%] of the 43 patients experienced grade 5 hematologic toxicity due to the regimen; 16 [37%], grade 4; and 10 [23%], grade 3). Local-regional control was 92% (23 of 25 patients), and the distant metastatic 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 systemic toxicity was unacceptable. Thus, the paclitaxel was changed to a weekly regimen.