KEY POINTS
- The study is designed as a single-centre, placebo-controlled, double-blind phase II trial enrolling 100 patients with locally advanced T3–4, node-positive, M0 esophageal squamous cell carcinoma.
- Participants will be randomized 1:1 to intravenous tetrandrine or matched placebo. Tetrandrine will be administered at 200–300 mg daily, six days per week, for 12 weeks.
- All patients will receive definitive IMRT to 50–50.4 Gy in 1.8 Gy fractions with concurrent docetaxel and cisplatin. At least 95% of the planning target volume should receive the prescribed dose, with daily cone-beam CT verification.
- Planned pulmonary constraints include lung V20 ≤30%, V5 below 63%, and mean lung dose below 20 Gy. The protocol also mandates treatment-plan verification with a gamma pass rate above 98% using 3%/3 mm criteria.
- The primary endpoint is the incidence of grade 2 or higher radiation-induced lung injury according to CTCAE version 5. Secondary endpoints include any-grade injury, time to onset, pulmonary-function changes, chemoradiotherapy completion, safety, and adherence.
- The statistical design requires 40 evaluable patients per group and provides 80% power to detect a reduction from 25% to 10%. However, it uses a two-sided alpha of 0.20, confirming that this is a signal-seeking pilot rather than a definitive efficacy trial.
- The rationale partly derives from a retrospective 32-patient observation in which lung injury reportedly fell from 45% to 28% with tetrandrine. That uncontrolled result is highly vulnerable to bias, and recruitment to the randomized trial had not begun when the protocol was published.
CLINICAL TAKEAWAY
The protocol addresses an important toxicity, but there is currently no evidence that tetrandrine prevents radiation pneumonitis during esophageal chemoradiotherapy. The intervention should not be used prophylactically outside the study, particularly given the exploratory statistical design and limited existing safety evidence in this setting.