Tetrandrine injection for preventing radiation-induced lung injury in patients with locally advanced esophageal squamous cell carcinoma: a randomized controlled trial protocol.

BACKGROUND: Radiation-induced lung injury (RILI) is a common and dose-limiting toxicity in patients with locally advanced esophageal squamous cell carcinoma (ESCC) receiving concurrent chemoradiotherapy (CCRT). Effective prophylactic agents are lacking. Tetrandrine, a bisbenzylisoquinoline alkaloid, has shown anti-inflammatory and anti-fibrotic properties in preclinical studies. This randomized controlled trial aims to evaluate the efficacy and safety of tetrandrine injection for preventing RILI in this population. METHODS: This is a single-center, randomized, placebo-controlled, double-blind, phase II trial. A total of 100 eligible patients with locally advanced ESCC (T3-4N+M0) receiving definitive CCRT will be randomly assigned (1:1) to receive either intravenous tetrandrine (200-300 mg/day, 6 days per week for 12 weeks) or matching placebo. Radiotherapy dose is 50-50.4 Gy (1.8 Gy/fraction) using IMRT, with concurrent docetaxel/cisplatin. The primary endpoint is the incidence of grade ≥2 RILI according to CTCAE v5.0. Secondary endpoints include any-grade RILI, time to RILI onset, change in pulmonary function, and CCRT completion rate. Sample size calculation (40 evaluable per group) provides 80% power to detect a 15% absolute risk reduction (from 25% to 10%) with two-sided α=0.20. The protocol follows SPIRIT 2013 guidelines. Recruitment has not yet started. DISCUSSION: This trial will generate preliminary evidence on the efficacy of tetrandrine for preventing RILI in ESCC patients. By adopting internationally accepted radiotherapy doses (50-50.4 Gy) and stringent lung dose constraints (V20 ≤ 30%, MLD < 20 Gy), the study provides a robust framework for comparing outcomes with global literature. SYSTEMATIC REVIEW REGISTRATION: https://www.chictr.org.cn/bin/project/edit?pid=289682, identifier ChiCTR2500111007.