Twice-daily reirradiation for recurrent and second primary head-and-neck cancer with gemcitabine, paclitaxel, and 5-fluorouracil chemotherapy

Purpose: We previously demonstrated the efficacy of concurrent gemcitabine, paclitaxel, and 5-fluorouracil in conjunction with twice-daily (1.5-Gy) radiotherapy delivered on alternating weeks (TFGX₂) in locally advanced head-and-neck cancer. Here, we report the clinical outcome and late toxicity of TFGX₂ in a subset of patients previously irradiated to the head and neck. Methods and Materials: Twenty-nine previously irradiated patients, presenting with recurrent or second primary head-and-neck cancer, underwent TFGX₂. Twelve patients underwent attempted surgical resection before chemoradiotherapy, 10 of whom were left with no measurable disease. Patients with measurable disease received a median radiation dose of 72 Gy; those with no measurable disease received a median dose of 61 Gy. The cumulative dose ranged from 74.4 to 156.4 Gy (mean, 125.7 Gy; median, 131.0 Gy). Results: The median follow-up was 19.1 months (50.9 months for living patients). The 5-year overall survival rate was 34.5%, and the locoregional control rate was 54.5%. In patients with measurable disease at treatment, the 5-year overall survival and locoregional control rate was 26.3% and 45.1%, respectively, compared with 50.0% (p = 0.14) and 70% (p = 0.31), respectively, for those with no measurable disease. Measurable disease and radiation dose were highly statistically significant for overall survival and locoregional control on multivariate analysis. Of 14 patients assessable for late toxicity, 3 developed Grade 4-5, 8 Grade 2-3, and 3 Grade 0-1 toxicity. Conclusion: Aggressive reirradiation with chemotherapy in locally advanced head-and-neck cancer provides a chance for long-term cure at the expense of toxicity. Attempted surgical resection before chemoradiotherapy improved disease control and survival.