title: Temoporfin improves efficacy of photodynamic therapy in advanced biliary tract carcinoma: A multicenter prospective phase II study.
abstract: Photodynamic therapy using porfimer (P-PDT) improves palliation and survival in nonresectable hilar bile duct cancer. Tumoricidal penetration depth of temoporfin-PDT (T-PDT) is twice that of P-PDT. In a single-arm phase II study we investigated the safety, efficacy, survival time, and adverse events of T-PDT compared with previous data on P-PDT. Twenty-nine patients (median 71 [range 47-88] years) with nonresectable hilar bile duct cancer were treated with T-PDT (median 1 [range 1-4] sessions) plus stenting and followed up every 3 months. The PDT was well tolerated. In patients with occluded segments at baseline (n=28) a reopening of a median of 3 (range 1-7) segments could be achieved: n=16 local response and n=11 stable local disease, one progressive disease. Cholestasis and performance significantly improved when impaired at baseline. Time to local tumor progression was a median of 6.5 (2.7-41.0) months. Overall survival time was a median of 15.4 (range 4.4-62.4) months. Patients died from tumor progression (55%), cholangitis (18%), pneumonia (7%), hemobilia (7%), esophagus variceal hemorrhage (3%), and vascular diseases (10%). Adverse events were cholangitis (n=4), liver abscess (n=2), cholecystitis (n=2), phototoxic skin (n=5), and injection site reactions (n=7). Compared to previous P-PDT, T-PDT shows prolonged time to local tumor progression (median 6.5 versus 4.3 months, P<0.01), fewer PDT treatments needed (median 1 versus 3, P<0.01), a higher 6-month survival rate (83% versus 70%, P<0.01), and a trend for longer overall median survival (15.4 versus 9.3 months, P=0.72) yet not significantly different. The risk of adverse events is not increased except for (avoidable) subcutaneous phototoxicity at the injection site.
  
  
  CONCLUSIONS
  Temoporfin-PDT can safely be delivered to hilar bile duct cancer patients and results in prolonged patency of hilar bile ducts, a trend for longer survival time, and similar palliation as with P-PDT.
authors.affiliation: Department of Medicine I, Paracelsus Medical University/Salzburger Landeskliniken (SALK), Salzburg, Austria.
authors.forename: Andrej
authors.initials: A
authors.lastname: Wagner
authors.affiliation: Department of Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.|Clinic for Interdisciplinary Endoscopy, University Hospital, Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Ulrike W
authors.initials: UW
authors.lastname: Denzer
authors.affiliation: Institute of Pathology, Paracelsus Medical University/Salzburger Landeskliniken (SALK), Salzburg, Austria.
authors.forename: Daniel
authors.initials: D
authors.lastname: Neureiter
authors.affiliation: Department of Medicine I, Paracelsus Medical University/Salzburger Landeskliniken (SALK), Salzburg, Austria.|Institute of Physiology and Pathophysiology, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Tobias
authors.initials: T
authors.lastname: Kiesslich
authors.affiliation: Department of Internal Medicine IV, Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.|Department of Internal Medicine II, Krankenhaus der Barmherzigen Brueder, Eisenstadt, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Puespoeck
authors.affiliation: Academic Medical Centre, Department of Gastroenterology & Hepatology, Amsterdam, The Netherlands.
authors.forename: Erik A J
authors.initials: EA
authors.lastname: Rauws
authors.affiliation: Department of General and Visceral Surgery, Krankenhaus Barmherzige Schwestern Linz, Austria.
authors.forename: Klaus
authors.initials: K
authors.lastname: Emmanuel
authors.affiliation: Department of Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Nora
authors.initials: N
authors.lastname: Degenhardt
authors.affiliation: Doepfer University of Applied Sciences, Cologne, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Frick
authors.affiliation: Academic Medical Centre, Department of Gastroenterology & Hepatology, Amsterdam, The Netherlands.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Beuers
authors.affiliation: Department of Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Ansgar W
authors.initials: AW
authors.lastname: Lohse
authors.affiliation: Department of Medicine I, Paracelsus Medical University/Salzburger Landeskliniken (SALK), Salzburg, Austria.
authors.forename: Frieder
authors.initials: F
authors.lastname: Berr
authors.affiliation: Department of Medicine I, Paracelsus Medical University/Salzburger Landeskliniken (SALK), Salzburg, Austria.
authors.forename: Gernot W
authors.initials: GW
authors.lastname: Wolkersdörfer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001661:Biliary Tract Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D001663:Bilirubin / Q000097:blood; D002423:Cause of Death; D005260:Female; D006801:Humans; D008297:Male; D008652:Mesoporphyrins / Q000627:therapeutic use*; D008875:Middle Aged; D010778:Photochemotherapy / Q000009:adverse effects
chemical_list: D008652:Mesoporphyrins; C072269:temoporfin; D001663:Bilirubin