Phase I study of photodynamic therapy using talaporfin sodium and diode laser for local failure after chemoradiotherapy for esophageal cancer

Tomonori Yano,Koji Higashino,Yusuke Yoda,Hogara Nishisaki,Kenichi Yoshimura,Yoshinobu Yamamoto,Manabu Muto,Yasumasa Ezoe,Hiroyasu Iishi,Miyuki Niimi

doi:10.1186/1748-717x-7-113

Abstract

BackgroundPhotodynamic therapy (PDT) is a less invasive and effective salvage treatment for local failure after chemoradiotherapy (CRT) for esophageal cancer, however it causes a high rate of skin phototoxicity and requires a long sun shade period. Talaporfin sodium is a rapidly cleared photosensitizer that is expected to have less phototoxicity. This study was undertaken to clarify the optimum laser fluence rate of PDT using talaporfin sodium and a diode laser for patients with local failure after CRT or radiotherapy (RT) for esophageal cancer.MethodsThis phase I, laser dose escalation study used a fixed dose (40 mg/m2) of intravenous talaporfin sodium administered 4 to 6 hours before irradiation in patients with local failure limited to T2 after CRT or RT (≥ 50 Gy). The primary endpoint was to assess the dose limiting toxicity (DLT) of PDT, and the secondary endpoints were to evaluate the adverse events and toxicity related to PDT. The starting fluence of the 664 nm diode laser was 50 J/cm2, with an escalation plan to 75 J/cm2 and 100 J/cm2.Results9 patients with local failure after CRT or RT for ESCC were enrolled and treated in groups of 3 individuals to the third fluence level. No DLT was observed at any fluence level. Phototoxicity was not observed, but one subject had grade 1 fever, three had grade 1 esophageal pain, and 1 had grade 1 dysphagia. Five of 9 patients (55.6%) achieved a complete response after PDT.ConclusionsPDT using talaporfin sodium and a diode laser was safe for local failure after RT in patients with esophageal cancer. The recommended fluence for the following phase II study is 100 J/cm2.

Highlights

Photodynamic therapy (PDT) is a less invasive and effective salvage treatment for local failure after chemoradiotherapy (CRT) for esophageal cancer, it causes a high rate of skin phototoxicity and requires a long sun shade period
Salvage esophagectomy is generally indicated in such cases, it carries with it a high morbidity and mortality [2,3,4,5]
Onozawa et al reported that regional nodal failure within the field of elective lymph node irradiation was rare in patients achieving a complete response (CR) after CRT (1%; 95% confidence interval [CI], 0%–5%) for esophageal squamous cell carcinoma (ESCC) [6]. These data might indicate that if both lymph node and distant metastasis were controlled by CRT, local salvage treatment that targeted only the primary site could be a minimally invasive curative treatment option in carefully selected patients. To develop such a treatment option for local failure, we have introduced photodynamic therapy (PDT) as a salvage treatment [7,8], and reported the results of the phase II study of salvage PDT for local residual T1 tumors after CRT [9]

Summary

Introduction

Photodynamic therapy (PDT) is a less invasive and effective salvage treatment for local failure after chemoradiotherapy (CRT) for esophageal cancer, it causes a high rate of skin phototoxicity and requires a long sun shade period. This study was undertaken to clarify the optimum laser fluence rate of PDT using talaporfin sodium and a diode laser for patients with local failure after CRT or radiotherapy (RT) for esophageal cancer. Methods: This phase I, laser dose escalation study used a fixed dose (40 mg/m2) of intravenous talaporfin sodium administered 4 to 6 hours before irradiation in patients with local failure limited to T2 after CRT or RT (≥ 50 Gy). 76% (19/25) of the patients could achieve CR and suffered only modest rates of adverse events and complications

Methods

Results

Conclusion