Improved efficacy of temoporfin photodynamic therapy in locally advanced biliary tract carcinoma: a multicenter prospective phase II study

Abstract

Introduction: Photodynamic therapy using porfimer (P-PDT) is established local tumor ablative therapy in non-resectable hilar bile duct cancer (hBDC) improving palliation and survival time. Tumoricidal penetration depth is only 4 mm with P-PDT, but at least 8 mm with temoporfin PDT (T-PDT). Aim: Therefore, we investigated in a single-arm phase II study (NCT01016002; from 2005 to 2011) non-inferiority of T-PDT vs. previous P-PDT in OS, local tumor control (TTP), and adverse events (ADE). Material and Patients: Patients (n = 29) with unresectable hBDC received median 1.0 (range 1 – 4) T-PDT plus stenting and were followed up at three-month intervals. Results: OS after treatment was median 17.3 (12.6 – 22.0, 95% CI) mon for 19 patients of category M0, and 15.4 mon for all patients (M0 + M1, 11.7 – 19.1, 95% CI). Median time to local tumor progression was 6.5 months (3.6 – 9.4, 95% CI). Cholestasis improved significantly in patients with initially elevated bilirubin levels and 74% of patients with occluded segments at baseline showed local response with reopening of median 3.0 segments. A significant improvement of palliation could be achieved (median +10%, range -20% – +40%). PDT was technically successful in all cases and was generally well tolerated; there was no grade 4 toxicity and no treatment-associated mortality. Adverse events were phototoxic skin reactions (n = 9), three late phototoxic skin reactions (at T-injected vein), cholangitis (n = 4), and liver abscess (n = 1). Conclusions: T-PDT can be delivered safely to patients with biliary tract cancer and shows improved time to treatment patency and prolonged survival compared to P-PDT. It is statistically not inferior to P-PDT concerning improvement of cholestasis and palliation. It is highly tumoricidal and associated with similar rates of infectious complications, but with an elevated rate of skin phototoxicity, which could have been possibly avoided, taking specific precautions.