Phase 2 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 Radiation Therapy Oncology Group Protocol 9911.

Purpose: 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 2 trial of split-course radiation therapy (RT) and concurrent paclitaxel and cisplatin.

Methods And Materials: 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/mevery day × 5) and paclitaxel (20 mg/mevery 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.

Results: 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).

Conclusions: 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.