talaporfin and Esophageal-Neoplasms

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.

Topics: Aged; Aged, 80 and over; Chemoradiotherapy; Esophageal Neoplasms; Female; Follow-Up Studies; Humans; Lasers, Semiconductor; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Photochemotherapy; Photosensitizing Agents; Porphyrins; Prognosis; Radiotherapy; Salvage Therapy; Survival Rate

Photodynamic 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.. 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). 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.. 9 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.. PDT 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.

Topics: Aged; Aged, 80 and over; Chemoradiotherapy; Esophageal Neoplasms; Humans; Lasers, Semiconductor; Male; Middle Aged; Neoplasm Recurrence, Local; Photochemotherapy; Photosensitizing Agents; Porphyrins; Salvage Therapy

Salvage photodynamic therapy with talaporfin sodium has a high local control rate for esophageal cancer after definitive chemoradiotherapy. The eligibility criteria for photodynamic therapy include the absence of invasion to the cervical esophagus and a 3 cm maximum longitudinal lesion length. There is little evidence regarding the efficacy and safety of lesions outside the eligibility criteria. This retrospective cohort study evaluated the efficacy and safety of photodynamic therapy of such lesions.. Patients with consecutive lesions between February 2016 and May 2020 (n = 36) were enrolled. The local complete response rates and adverse events were compared between patients with cervical and non-cervical lesions and those with lesions larger and smaller than 3 cm.. The local complete response rate was 77.8% and was significantly lower in cervical than in non-cervical lesions (20.0% vs 80.6%, p = 0.005). Esophageal stricture, laryngeal pain, and fever were significantly higher in the cervical than in the non-cervical lesion group; however, the detected adverse events were up to grade 2. Laser exposure dose was high in lesions larger than 3 cm (median, 650 vs 400 J; p < 0.001). No significant differences in local complete response rates and adverse effects were noted. One case involving a lesion larger than 3 cm needed balloon dilations for esophageal stricture.. Although salvage esophageal photodynamic therapy was effective for local control with acceptable safety after definitive chemoradiotherapy failure, photodynamic therapy toward cervical lesions had a statistically lower local complete response rate. Lesions larger than 3 cm may be considered treatable.

Topics: Esophageal Neoplasms; Humans; Photochemotherapy; Photosensitizing Agents; Porphyrins; Retrospective Studies

Talaporfin sodium photodynamic therapy (tPDT) is an effective salvage treatment for local failure after chemoradiotherapy for esophageal cancer. Repeated tPDT could also be indicated for local recurrence or residue after the first salvage tPDT. However, the safety and efficacy of repeated tPDT have not been elucidated.. We reviewed 52 patients with esophageal cancer who were treated with the first tPDT at Kyoto University Hospital between October 2015 and April 2020.. Among 52 patients, repeated tPDT after the first tPDT was indicated for 13 patients (25%), of which six had residual tumor, four had local recurrence after complete response (CR) after the first tPDT at the primary site, and six had metachronous lesion. The total session of repeated tPDT was 25; 16 were for primary sites and nine were for metachronous sites. Among them, six patients (46.2%) achieved local (L)-CR and nine lesions (56.3%) achieved lesion L-CR. By session, 10 sessions (40%) achieved L-CR. There were no severe adverse events except for one patient; this patient showed grade 3 esophageal stenosis and perforation after the third tPDT on the same lesion that was previously treated with porfimer sodium photodynamic therapy four times.. Repeated tPDT could be an effective and safe treatment for local failure even after salvage tPDT for esophageal cancer.

Topics: Carcinoma, Squamous Cell; Esophageal Neoplasms; Humans; Neoplasm Recurrence, Local; Photochemotherapy; Porphyrins

Photodynamic therapy (PDT) is a salvage treatment for local failure following chemoradiotherapy (CRT) for esophageal cancer. This study aimed to evaluate the efficacy and safety of salvage PDT using the second-generation photosensitizer, talaporfin sodium (L-PDT), and compare L-PDT to PDT using porfimer sodium (P-PDT).. We retrospectively analyzed clinical outcomes of patients treated with L-PDT and P-PDT. Patients with histologically proven local failure limited to the shallow muscularis propria layer (T2) after CRT or radiotherapy (RT) for esophageal cancer were enrolled.. A total of 121 patients were enrolled in this study. L-PDT and P-PDT groups consisted of 44 and 77 patients, respectively. The overall local complete response (L-CR) rate was 62.1% (95% confidence interval [CI], 52.6-70.9), and the L-PDT group showed a better L-CR rate than did the P-PDT group (69.0% [95% CI 52.9-82.4] vs. 58.1% [95% CI 46.1-69.5]). The common complications of skin phototoxicity, esophageal stricture, and esophageal fistula were all less frequent in the L-PDT group than in the P-PDT group. The only treatment-related death in this study was in the P-PDT group. With a median follow-up period of 15.8 months (interquartile range 7.1-37.4) in all 121 patients, overall survival rate at 1 year was significantly higher among patients who achieved L-CR (91.2% [95% CI 80.2-96.3]) than among those who could not achieve L-CR with PDT (50.8% [95% CI 33.6-65.6]).. L-PDT represented better short-term outcomes than P-PDT as a salvage treatment for local failure following CRT or RT for esophageal cancer.

Topics: Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Chemoradiotherapy; Dihematoporphyrin Ether; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Photochemotherapy; Photosensitizing Agents; Porphyrins; Retrospective Studies; Salvage Therapy; Treatment Failure

Photodynamic therapy (PDT) kills cancer cells via a photochemical reaction mediated by an oncotropic photosensitizer. Herein, we performed an experimental preclinical study to validate the anti-tumour effect of talaporfin sodium-mediated PDT (t-PDT) for esophageal squamous cell carcinoma (ESCC) cells. We used human ESCC cells derived from various differentiation grades or resistant to 5-fluorouracil (5-FU). The cytotoxic effect of t-PDT was determined by evaluating cell viability, apoptosis and generation of reactive oxygen species (ROS) and DNA double-strand breaks. Furthermore, the anti-tumour effect of t-PDT was assessed using an anchorage-independent cell-growth assay and xenograft transplantation models. t-PDT induced potent cytotoxicity in ESCC cells independent of their differentiation grade or 5-FU resistance. Moreover, t-PDT induced robust apoptosis, as indicated by cell shrinkage, perinuclear vacuolization, nuclear fragmentation and induction of annexin V-positive cells. This apoptotic response was accompanied by concurrent activation of ROS, and induction of DNA double-strand breakage. Importantly, t-PDT suppressed efficiently anchorage-independent cell growth as well as ESCC-xenografted tumor formation. In aggregate, t-PDT showed anti-tumor potential for ESCC cells with various histological grades or chemoresistance, providing a novel translational rationale of t-PDT for the treatment of ESCC.

Topics: Animals; Apoptosis; Carcinoma, Squamous Cell; Cell Adhesion; Cell Line, Tumor; Cell Proliferation; DNA Breaks, Double-Stranded; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Fluorescence; Humans; Intracellular Space; Mice; Photochemotherapy; Porphyrins; Reactive Oxygen Species; Reproducibility of Results

To increase the applicability of photodynamic diagnosis with regard to deep-seated tumor, we illuminated tumors with a long-wavelength laser beam after photosensitization with mono-L-aspartyl chlorin e6 (NPe6).. Rabbits with VX2 esophageal tumors were divided into four groups. The control group was not treated, and the other three groups were injected with 1, 2.5, and 5 mg/kg mono-L-aspartyl chlorin e6 (NPe6), respectively. After excitation with a 664-nm laser beam (10 mW, 10 seconds), the fluorescence image and the relative fluorescence intensity (tumor/normal tissue) were recorded every 2 hours up to 8 hours by a newly developed diode laser endoscopic fluorescence imaging system. The tissue concentration of NPe6 was examined by high performance liquid chromatography at 2, 4, and 6 hours after injection with 1 and 5 mg/kg NPe6.. The diode laser endoscopic fluorescence imaging system was able to selectively detect fluorescence from submucosal tumor by comparison with the surrounding normal mucosa after NPe6 injection. The fluorescence intensity correlated with NPe6 dose, selectively accumulated in the tumor tissue and relative intensity peaked at 6 hours after injection. No fluorescent images were detected in controls.. Given intravenously, NPe6 at a dose of 5 mg/kg and excited with a 664-nm wavelength laser beam 6 hours later can define experimentally induced deep-seated esophageal carcinoma in rabbits, by using an endoscopic fluorescence imaging system.

Topics: Animals; Equipment Design; Esophageal Neoplasms; Esophagoscopy; Male; Mucous Membrane; Photochemistry; Photosensitizing Agents; Porphyrins; Rabbits