Concurrent Chemo-Radiation With or Without Induction Gemcitabine, Carboplatin, and Paclitaxel: A Randomized, Phase 2/3 Trial in Locally Advanced Nasopharyngeal Carcinoma

Purpose: To compare survival, tumor control, toxicities, and quality of life of patients with locally advanced nasopharyngeal carcinoma ( NPC) treated with induction chemotherapy and concurrent chemo- radiation ( CCRT), against CCRT alone. Patients and Methods: Patients were stratified by N stage and randomized to induction GCP ( 3 cycles of gemcitabine 1000 mg/ m 2, carboplatin area under the concentration- time- curve 2.5, and paclitaxel 70 mg/ m 2 given days 1 and 8 every 21 days) followed by CCRT ( radiation therapy 69.96 Gy with weekly cisplatin 40 mg/ m 2), or CCRT alone. The accrual of 172 was planned to detect a 15% difference in 5- year overall survival ( OS) with a 5% significance level and 80% power. Results: Between September 2004 and August 2012, 180 patients were accrued, and 172 ( GCP 86, control 86) were analyzed by intention to treat. There was no significant difference in OS ( 3- year OS 94.3% [ GCP] vs 92.3% [ control]; hazard ratio 1.05; 1- sided PZ. 494]), disease- free survival ( hazard ratio 0.77, 95% confidence interval 0.44- 1.35, PZ. 362), and distant metastasesefree survival ( hazard ratio 0.80, 95% confidence interval 0.38- 1.67, PZ. 547) between the 2 arms. Treatment compliance in the induction phase was good, but the relative dose intensity for concurrent cisplatin was significantly lower in the GCP arm. Overall, the GCP arm had higher rates of grades 3 and 4 leukopenia ( 52% vs 37%) and neutropenia ( 24% vs 12%), but grade 3 and 4 acute radiation toxicities were not statistically different between the 2 arms. The global quality of life scores were comparable in both arms. Conclusion: Induction chemotherapy with GCP before concurrent chemo- irradiation did not improve survival in locally advanced NPC. 2015 Elsevier Inc. All rights reserved.