Temoporfin photodynamic therapy in advanced hilar ductal carcinoma: A promising endoscopic modality
Authors: Nikhil A. Kumta, Ketisha DeRoche, Michel Kahaleh
Journal: Hepatology (2015)

Potential conflict of interest: Dr. Kahaleh consults and received grants from Boston Scientific, MaunaKea, and Xlumena. He consults for Concordia and received grants from Emcison, W.L. Gore, Apollo Endosurgery, ASPIRE Bariatrics, GI Dynamics, NinePoint, Merit, and MI Tech. See Article on Page 1456 Biliary hilar ductal tumors account for 2% of all cancers and remain a challenge to treat due to advanced stage at diagnosis.1 Hilar ductal carcinoma is the second most common malignancy arising from the liver, and survival time is approximately 3 months without any interventions.2 The only potential for cure is a complete resection with negative margins, and even then 5‐year survival rates are 40%‐60%, with a significant amount of patients eventually succumbing to the disease. Surgery was the traditional approach to palliative biliary decompression, though hepaticojejunostomy is associated with a 30‐day postoperative mortality rate of 7%‐24% with minimum improvement in quality of life.2 Solitary chemotherapy has been deemed ineffective, with a small survival rate of 1 month with a gemcitabine/cisplatin‐based combination. Palliative brachytherapy has not been shown to prolong survival time.3 Palliative endoscopic biliary stenting has become the favored modality to achieve decompression of the biliary tree, though it is limited by an inability to decompress proximal segments, recurrent occlusions, and an inability to remodel malignant tissue.2 Photodynamic therapy (PDT) is an endoscopic mode of palliation which uses photodynamic reactions producing oxygen free radicals to induce tumor destruction by vascular ischemia, apoptosis, and necrosis.1 Two randomized controlled trials have shown favorable outcomes using porfimer photodynamic laser therapy (P‐PDT) in patients with advanced biliary disease.4 One of these trials incorporated biliary stenting with PDT and showed significant improvement in quality of life.5 The mechanism of action is thought to be the inducing and prolonging of a decompressive effect, thereby remodeling the tumor mass.2 Relieving biliary obstruction is the mainstay of palliative therapy to avoid complications such as refractory empyematous cholangitis, biliary sepsis, and liver failure.1 PDT is effective at providing palliation in patients with advanced disease and has been shown to improve survival, quality of life, and performance status. In this issue of Hepatology, Wagner et al. conducted a single‐arm phase 2 trial evaluating the efficacy, safety, survival time, and adverse events of temoporfin PDT (T‐PDT) in patients with advanced biliary malignancies compared to previously published data on P‐PDT.7 Twenty‐nine patients with unresectable disease were enrolled and treated with T‐PDT and biliary stenting, then followed up every 3 months. The authors found that T‐PDT can be administered safely and is well tolerated. Compared to previous PDT data, T‐PDT patients had a statistically significant improvement in time to local tumor progression, higher 6‐month survival, and fewer PDT treatments needed. There was a trend for longer overall median survival, though this was not significantly different. The results from the study also indicated that reopening of occluded segments was possible. This is likely attributed to the depth of therapeutic tumor penetration with T‐PDT. Compared with P‐PDT, which penetrates up to a maximum of 4‐6 mm, photosensitization with temoporfin can reach up to 9 mm with higher quantum yields and activation at longer wavelengths.8 There are some limitations that should be noted. The study was designed to compare T‐PDT results to a historical cohort of patients treated with P‐PDT. The study is also limited by the small sample size. All patients were stented prior to the study and had only minimal elevation in bilirubin. PDT is associated with a reduction in bilirubin, which increases survival time.2 The results of this multicenter phase 2 trial using temoporfin to enhance PDT in advanced biliary tumors are promising due to the safe administration of T‐PDT without any significant increase in adverse effects and statistically significant improvements in time to local tumor progression, higher 6‐month survival, and fewer PDT treatments needed. We are encouraged by the data presented in this study and eagerly await decisive phase 3 testing.