Optimization of sinoporphyrin sodium (DVDMS)-mediated photodynamic therapy (PDT) in patients (pts) with advanced esophageal cancer (EC): A multicentre phase II single-arm clinical trial.
Authors: Zhou Jun , Lu Zhihao , Yuan Jiajia , Cao Yanshuo , Gao Shegan , Shu Yongqian , Chen Hao , Fan Huizhen , Zhang Hao , Dong Caihong , Shan Tanyou , Shen Lin 
Published: July 2024

e16042

Background: Esophageal stenosis (ES) or dysphagia is a common symptom of advanced EC, 90% of pts seen dysphagia as a principal symptom, of which early and sustained relief predicts better prognosis. PDT is a local treatment for the control of ES and dysphagia symptoms. DVDMS, a new type of photosensitizer, offers the advantages of high activity at low dosage and low phototoxicity. This study aims to investigate the effectiveness and safety of DVDMS-mediated PDT, and to provide a basis for subsequent optimization for the light dose on PDT treatment of dysphagia in advanced EC. Methods: This phase II trial included advanced EC pts with ≥ grade 2 dysphagia, who were not suitable for or declined curative therapies (CTR20200598). Previous phase I study determined 0.2 mg/kg as the recommended phase 2 dose using the light dose of 102 J/cm with a 24-hour-interval from DVDMS injection. In this trial, 0.2 mg/kg DVDMS was administrated followed by PDT (wavelength: 630 nm) at 200 J/cm or 102 J/cm with a time interval of 24h from DVDMS injection. The primary endpoint was esophageal stenosis overall response rate (es-ORR), including complete (no visible tumor on endoscopy) and partial remission (increase ≥ 50% in the minimum diameter of ES). Results: As of 12 December 2022, 6 pts were enrolled in 200 J/cm 24 h group, and 20 in 102 J/cm 24 h group. At day 28, the es-ORR was 50% (3/6) and 40% (8/20), the es-disease control rate was 83.3% and 90%, respectively. At day 28, the mean minimum diameter of ES increased by 3.50±2.000 mm (67.143%) and 2.06±2.940 mm (45.936%) from the baseline, respectively; while the dysphagia symptoms improved or stabilized in all pts (100%) and the improved rate was 66.7% and 35.3%, respectively. The reduction in Stooler's Dysphagia Score from baseline was 0.7±0.52 and 0.4±0.49 points, respectively, and the improvement sustained at 6 months (reduction: 1.0±1.00 and 0.7±0.49 points; improved rate: 66.7% and 71.4%, respectively). The esophageal stenosis median duration of response was 5.13 (95% CI: 4.50, not estimable [NE]) and 3.48 (95% CI: 0.95, NE) months in the 200 J/cm group and 102 J/cm group, while the median overall survival was 10.46 (95% CI: 2.96, NE) months and 9.84 (95% CI: 4.80, NE) months, respectively. DVDMS-related adverse events (AEs) occurred in 0% and 30% in the 200 J/cm and 102 J/cm groups, respectively, all grades 1-2. PDT-related AEs occurred in 100% and 85% (≥ grade 3: 33.3% and 10.0%), respectively. Treatment-emergent AEs leading to death occurred in 4 pts (2 in the 200 J/cm and 2 in the 102 J/cm groups), not related to DVDMS or PDT. On day 4, phototoxicity was positive in 2 (33.3%) and 7 (35.0%) pts in the 200 J/cm and 102 J/cm groups, and negative in all pts on day 28. Conclusions: DVDMS-mediated PDT in pts with advanced EC improves ES and symptoms of dysphagia, with a rapid onset, sustained efficacy, and good tolerability. Clinical trial information: CTR20200598.