Phase II Study of Low-Dose Paclitaxel and Cisplatin in Combination With Split-Course Concomitant Twice-Daily Reirradiation in Recurrent Squamous Cell Carcinoma of the Head and Neck: Long-term Follow-up of NRG Oncology RTOG 9911.

Abstract

Locoregionally recurrent squamous cell carcinoma of the head and neck and second primary tumors (SPTs) in previously irradiated fields, if not resectable, are virtually always fatal. Chemotherapy alone yields a median survival of 10 to 11 months and 5-year overall survival (OS) rates of <5%. Concurrent reirradiation and chemotherapy constitutes an alternative, nonstandard strategy. Herein, we report the long-term outcomes of NRG Oncology Radiation Therapy Oncology Group 9911, a phase II trial of split-course radiation therapy (RT) and concurrent paclitaxel and cisplatin. Eligibility stipulated measurable, recurrent squamous cell carcinoma of the head and neck or SPT in previously irradiated fields, performance status 0-1, and adequate end-organ indices. Patients received split course, twice-daily RT (1.5 Gy/fraction twice a day × 5 days every 2 weeks ×4), plus cisplatin (15 mg/m²every day × 5) and paclitaxel (20 mg/m²every day ×5) every 2 weeks for 4 cycles. Granulocyte colony-stimulating factor was administered on days 6 to 13 of each 2-week cycle. The primary endpoint was OS relative to historical control, NRG Oncology Radiation Therapy Oncology Group 9610. Secondary endpoints included progression-free survival, toxicities, and patterns of failure. Between March 2000 and June 2003, 105 patients were enrolled; 100 patients were analyzable (76% male, median age 60 years). Oropharynx (41%) and oral cavity (27%) were the predominant primary sites. A total of 23% had SPT. Median prior RT dose was 65.7 Gy. Overall, 73% of patients completed all chemotherapy. Nine treatment-related deaths (9%) occurred: 5 in the acute and 4 in the late setting. Survival was significantly improved over historical control (P = .01) with 5-year survival increased from 3.8% (95% CI, 0.0-8.0) to 14.9% (95% CI, 7.9-21.9). Five-year progression-free survival was 7.0% (95% CI, 2.0-12.0). A total of 64.9% died of incident cancer, 3.2% of SPT, and 22.3% of noncancer or unknown causes. In 1-year survivors, the rate of subsequent late grade 4-5 toxicity was significantly higher than historical control (P = .02), with 5-year cumulative incidence of 22.4% (95% CI, 11.8-35.1) compared with 3.2% (95% CI, 0.2-14.5). Despite a high incidence of grade 5 toxicity, OS rates for this trial evaluating concurrent split course twice a day reirradiation with cisplatin and paclitaxel exceeded results seen historically with chemotherapy alone.