Randomized Phase II Trial of Gemcitabine and Cisplatin (GP) versus Docetaxel and Cisplatin (TP) as Induction Chemotherapy followed by Concurrent Chemoradiotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma

GP as induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) has been confirmed as effective regimen in endemic locoregionally advanced NPC (LA-NPC). A randomized phase II study reported that neoadjuvant TP followed by CCRT had a trend to improve survival outcomes in LA-NPC. Little is known about the best regime for induction chemotherapy in non-endemic region. This randomized phase II trial compared GP versus TP regime followed by concurrent chemoradiotherapy in LA-NPC of Northwest China (clinical trial No.: NCT01596868). Previously untreated stage III to IV LA-NPC were randomly assigned in 1:1 ratio to receive ⑴ neoadjuvant docetaxel 75mg/m2 and cisplatin 80mg/m2 every 3 weeks for three cycles, followed by cisplatin 100mg/m2 concurrent with radiotherapy, administered every three weeks for three cycles, or ⑵neoadjuvant gemcitabine 1.0g/m2 and cisplatin 80mg/m2 every 3 weeks for three cycles, followed by cisplatin 100mg/m2 concurrent with radiotherapy, administered every three weeks for three cycles. The primary endpoint was treatment response of induction chemotherapy. The secondary endpoints included disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS), locoregional recurrence-free survival (LRFS) and toxicities. Tumor response was assessed by RESIST criteria. Assuming the treatment response rate of 40% in TP group, approximately 50 patients in each group would be enrolled to detect a difference of 25% at the significance level of 5% (two-sided) with 80% power. The Kaplan-Meier method was used to evaluate the efficacy between treatment groups. A 2-sided p value of less than 0.05 was considered significant. From December 2012 to December 2016, 109 eligible patients were randomly assigned to GP followed by CCRT (n = 54) or TP followed by CCRT (n = 55).The median follow-up time was 45.5 months (range:6-60.5 months).A total of 105 patients (96.3%) completed three cycles of induction chemotherapy, 4 patients(3.7%)completed two cycles of induction chemotherapy due to grade 3 and above adverse events. During induction chemotherapy course, GP contributed toa higher treatment response rate than TP in primary tumor(68.6% vs. 38.2%, p = 0.013) and lymph node (90.8% vs. 74.5%, p = 0.045).Patients in GP group have significantly better 3-year DFS than those in TP group (86.8% vs. 70.9%, p = 0.041). Although significant differences were not achieved, GP plus CCRT had a trend in improving 3-year OS, DMFS and LRFS compared with TP plus CCRT (3-year OS, 90.6% vs. 83.6%, p = 0.118;3-year DMFS, 88.7% vs. 78.2%, p = 0.137;3-year LRFS, 96.2% vs. 92.7%, p = 0.085). No significant difference of adverse events was observed between two treatment groups during both the induction chemotherapy and concurrent chemoradiotherapy course. Compared with TP induction chemotherapy, GP significantly improved the treatment response rate and DFS among patients with LA-NPC.