title: Photodynamic therapy for hilar bile duct cancer: clinical evidence for improved tumoricidal tissue penetration by temoporfin.
abstract: Photodynamic therapy (PDT) has been established for palliation of non-resectable hilar bile duct cancer (hBDC). Ablation of hBDC using porfimer (P-PDT) improves cholestasis and survival. However, the tumoricidal effect is confined to the inner 4 mm of the tumor wall. Here, we have studied whether temoporfin PDT (T-PDT) shows an efficient local response and an increased tumoricidal penetration depth. In the first stage of a phase-II trial (NCT01016002), eleven patients with hBDC (Bismuth III-IV) were treated with T-PDT plus stenting and 10 could be analyzed for local tumor response. T-PDT resulted in complete local response in n = 1 of 10 patients, partial response in n = 8 and no response in one patient (occluded right hepatic duct re-opened but positive for residual tumor cells) - indicating a tumoricidal efficacy of 90%. Four patients showed a tumoricidal depth of ≥7.5 mm. Cholestasis and palliation improved in 8 patients with an overall median survival of 18 (4.4-32.0) months after the first T-PDT. Adverse events were phototoxic skin reaction (n = 4), cholangitis (n = 3), and liver abscess (n = 3). T-PDT doubles the depth of the local tumor-ablative effect of P-PDT, is highly tumoricidal and is associated with similar rates of infectious complications and grade I and II skin phototoxicity.
authors.affiliation: Department of Internal Medicine I, Paracelsus Medical University/Salzburger Landeskliniken (SALK), Salzburg, Austria.
authors.forename: Andrej
authors.initials: A
authors.lastname: Wagner
authors.forename: Tobias
authors.initials: T
authors.lastname: Kiesslich
authors.forename: Daniel
authors.initials: D
authors.lastname: Neureiter
authors.forename: Paul
authors.initials: P
authors.lastname: Friesenbichler
authors.forename: Andreas
authors.initials: A
authors.lastname: Puespoek
authors.forename: Ulrike W
authors.initials: UW
authors.lastname: Denzer
authors.forename: Gernot W
authors.initials: GW
authors.lastname: Wolkersdörfer
authors.forename: Klaus
authors.initials: K
authors.lastname: Emmanuel
authors.forename: Ansgar W
authors.initials: AW
authors.lastname: Lohse
authors.forename: Frieder
authors.initials: F
authors.lastname: Berr
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001650:Bile Duct Neoplasms / Q000188:drug therapy* / Q000473:pathology; D001652:Bile Ducts / Q000187:drug effects* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008652:Mesoporphyrins / Q000627:therapeutic use*; D008875:Middle Aged; D010778:Photochemotherapy / Q000009:adverse effects; D017319:Photosensitizing Agents / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D008652:Mesoporphyrins; D017319:Photosensitizing Agents; C072269:temoporfin