Predictors of response and survival after concurrent chemotherapy and radiation for locally advanced squamous cell carcinomas of the head and neck

BACKGROUND. The objective of this study was to determine prognostic factors for response and survival on three consecutive institutional trials utiliz ing concurrent chemotherapy and radiation for locally advanced squamous cel l carcinomas of the head and neck (SCCHN). METHODS. Since 1985, patients with locally advanced SCCHN at the University of Maryland have been managed with concurrent chemotherapy and radiation t herapy (RT). Three consecutive pilot studies have been performed evaluating the utility of weekly chemotherapy with standard fractionated RT. Chemothe rapy consisted of carboplatin either alone (28 patients) or in combination with bleomycin (23 patients) or paclitaxel (GO patients). In all three stud ies, RT was given to 70.2 gray (Gy) at 1.8 Gy/fraction/day to the primary s ite. All patients had locally advanced SCCHN and were believed to be poor s urgical candidates. Sixty-seven percent of patients had T4 disease, and 21% had T3 disease. Seventy-five percent of patients had N2-N3 discase. One hu ndred eleven patients were examinable for toxicity, response, and survival analysis. Factors including age, race, gender, primary site location, histo logic grade, T classification, N classification, and treatment regimen were evaluated to identify predictors of these endpoints. RESULTS. The median follow-up for patients treated on study 1 (carboplatin and RT) and study 2 (carboplatin and bleomycin [C + B/RT) was 98 months, an d it was 30 months for study 3 (carboplatin and paclitaxel [C +; P/RT). The complete response rates were 54%, 52%, and 70% respectively (P = 0.01). Mu ltivariate analysis identified length of treatment break (< 1 week vs. > 1 week) as the only predictor of complete response to therapy. The local cont rol for the entire group was 50%. The local control for C + P/RT was 63%, v ersus 32% and 36% for C/RT and C + B/RT respectively (P = 0.004). The 2-, 3 -, and 5-year disease free and overall survivals for the entire population were 41%, 41%, and 35% and 42%, 36% and 33%, respectively. The 3-year overa ll survival rates by treatment regimen were 18% (C/RT), 35% (C + B/RT), and 47% (C + P/RT; P = 0.01). On univariate analysis, age younger than 50 year s (P = 0.01), treatment with C + P/RT (P = 0.005), and treatment break of 5 days or fewer (P < 0.05) were also predictive of improved overall survival . On multivariate analysis, only complete response (P < 0.0001) and treatme nt with C + P/RT (P = 0.02) remained statistically significant. CONCLUSIONS. Chemoradiation provides patients with locally advanced SCCHN t he opportunity for long term survival. Among the three chemoradiation regim ens studied, C + P/RT was associated with the best complete response and su rvival rates. Complete response to therapy was the single most important pr edictor of overall survival. These three consecutive concurrent chemotherap y and radiation trials achieved a 5-year survival of greater than 30% for t he entire population. These results support the use of this nonoperative ap proach for this group of patients with a historically poor prognosis. (C) 2 001 American Cancer Society.