A multicenter phase II study of salvage photodynamic therapy using talaporfin sodium (ME2906) and a diode laser (PNL6405EPG) for local failure after chemoradiotherapy or radiotherapy for esophageal cancer

Abstract

Photodynamic therapy (PDT) showed promising efficacy for local failure after chemoradiotherapy (CRT) for esophageal cancer. However, PDT required long sun shade period. This study aimed to evaluate the safety and efficacy of PDT using second generation photosensitizer, talaporfin sodium for local failure after CRT. This was the multi-institutional non-randomized phase II study. Patients with histologically proven local failure limited within the muscularis propria after 50Gy or more radiotherapy (RT) for esophageal cancer were eligible. We set the primary endpoint as local complete response (L-CR) per patients. And, secondary endpoints were confirmed L-CR, local progression free survival (L-PFS), progression free survival (PFS), overall survival (OS), L-CR per lesions (Lesion L-CR), and confirmed Lesion L-CR. The PDT procedure commenced with intravenous administration of a 40 mg/m2 dose of talaporfin sodium followed by diode laser irradiation at a 664 nm wavelength. 26 eligible patients were enrolled and all were treated with PDT. Twenty three patients with 25 lesions were assessed L-CR after PDT; the L-CR rate per patients was 88.5% (95% CI: 69.8%-97.6%). No skin phototoxicity was observed, and no grade 3 or worse non-hematological toxicities related to PDT were observed. PDT using talaporfin sodium and a diode laser is a safe and curative salvage treatment for local failure after CRT or RT for patients with esophageal cancer.

Photodynamic therapy for solid tumors: A review of the literature

“…Progression‐free survival and overall survival for 113 patients treated with salvage PDT were 22.1 and 35.9%, respectively, for a mean follow‐up period of 5 years, with low phototoxicity rates . A recent study showed 88.5% (95% CI 69.8%‐97.6%) of 23 patients achieving local complete response after salvage PDT with talaporfin sodium and a diode laser, with no skin phototoxicity observed . These studies demonstrate increasing promise of talaporfin sodium PDT as a potential curative salvage treatment for patients failing CRT.…”

Role of photodynamic therapy in the treatment of esophageal cancer

“…After that, a phase I study of talaporfin PDT to find the adequate laser dose for esophageal cancer was conducted, and no patient experienced severe adverse events or phototoxicity, supporting the establishment of 100 J/cm 2 as the recommended dose for treating local failure after CRT . Subsequently, a multi‐institutional phase II study to acquire regulatory approval was conducted in Japan . The PDT procedure commenced with i.v.…”

“…Therefore, in the trial of PDT using talaporfin sodium patients with baseline T4 aorta invasion before radiotherapy or lesions larger than 3 cm or half circumference of lumen were excluded. According to the revised criteria, no cases of esophageal perforation or stricture were reported in the trial of PDT with talaporfin sodium …”

“…60 Subsequently, a multi-institutional phase II study to acquire regulatory approval was conducted in Japan. 61 The PDT procedure commenced with i.v. administration of 40 mg/m 2 dose of talaporfin sodium followed by laser illumination at a 664-nm wavelength 4-6 h after administration in 26 patients with 28 histologically confirmed lesions (T1b, 21; T2, 7).…”

“…According to the revised criteria, no cases of esophageal perforation or stricture were reported in the trial of PDT with talaporfin sodium. 61 It is important to assess the depth of the lesion and determine its distance from large arteries before treatment, especially when using talaporfin sodium, because it uses a longer wavelength of laser compared with first-generation PDT. The most significant different complication between these two agents must be the skin phototoxicity.…”