GP regimen chronomodulated induction chemotherapy combined with concurrent chemoradiotherapy for locally advanced nasopharyngeal carcinoma: A phase III, multicenter, randomized controlled study.

Abstract

TPS6137 Background: Radiotherapy is the primary treatment for nasopharyngeal carcinoma (NPC). Currently, induction chemotherapy combined with concurrent chemoradiotherapy has become a Category I recommendation for NPC treatment. Studies show that the GP regimen is one of the most effective induction chemotherapy protocols for locally advanced NPC. However, the incidence of grade 3-4 acute toxicities with the GP regimen is as high as 75.7%, severely affecting patient treatment compliance. To reduce toxicity while maintaining efficacy, this study focuses on a "chronomodulated chemotherapy" strategy, which adjusts drug administration timing based on biological rhythms to minimize damage to normal tissues. Methods: Clinical Data: 1. Sample Size Calculation: This study is a randomized controlled trial with a non-inferiority design. Based on a 3-year recurrence-free survival rate of 85.3% in the conventional group, a non-inferiority margin (δ) of 10%, a one-sided α of 0.025, a power (1-β) of 0.8, equal group sizes, and accounting for a 10% dropout rate, the calculated total sample size is 434 subjects. 2. Inclusion Criteria: Treatment-naïve patients with Stage III or IVa non-keratinizing nasopharyngeal carcinoma (UICC/AJCC 8th edition). 3. Exclusion Criteria: History of prior malignancy, prior radiotherapy, or presence of other severe diseases. 4. Withdrawal Criteria: Occurrence of severe adverse events or intolerable toxicities during the study. Treatment Protocol: 1. Induction Chemotherapy Phase: Experimental Group: Gemcitabine 1000 mg/m², IV infusion over 30 min on days 1 & 8, administered between 08:00-09:30; Cisplatin 80 mg/m², continuous IV infusion (civ) on day 1, delivered evenly over 12 h from 10:00 to 22:00. Repeated every 3 weeks (Q3W) for 3 cycles. Control Group: Gemcitabine 1000 mg/m², IV infusion over 30 min on days 1 & 8; Cisplatin 80 mg/m², IV infusion over 2-3 h on day 1. Q3W for 3 cycles. 2. Concurrent Chemoradiotherapy Phase: Concurrent Cisplatin Regimen: Experimental Group: Cisplatin 100 mg/m², civ on day 1, delivered evenly over 12 h from 10:00 to 22:00. Q3W for 3 courses. Control Group: Cisplatin 100 mg/m², IV infusion over 2-3 h on day 1. Q3W for 3 courses. 3. Radiotherapy: Intensity-Modulated Radiation Therapy (IMRT) was used, with a total dose of 69.96-72.6 Gy delivered in 33 fractions. Innovation: Therapeutic efficacy for nasopharyngeal carcinoma has reached a plateau, making “toxicity reduction” a key research focus. The toxicity-reducing approach of chronomodulated chemotherapy holds promising application prospects for locally advanced nasopharyngeal carcinoma. Current Status: To date, 122 patients have been enrolled. Clinical trial information: ChiCTR2400086032.