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Photodynamic therapy for hilar bile duct cancer: clinical evidence for improved tumoricidal tissue penetration by temoporfin

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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.

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Authors and Affiliations

  1. Department of Internal Medicine I, Paracelsus Medical University/Salzburger Landeskliniken (SALK), Muellner Hauptstrasse 48, 5020, Salzburg, Austria

    Andrej Wagner, Tobias Kiesslich, Paul Friesenbichler, Gernot W. Wolkersdörfer & Frieder Berr

  2. Institute of Pathology, Paracelsus Medical University/Salzburger Landeskliniken (SALK), Salzburg, Austria

    Tobias Kiesslich & Daniel Neureiter

  3. Department of Internal Medicine IV, Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria

    Andreas Puespoek

  4. Clinic for Interdisciplinary Endoscopy, University Hospital, Hamburg-Eppendorf, Hamburg-Eppendorf, Hamburg, Germany

    Ulrike W. Denzer

  5. I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany

    Ulrike W. Denzer & Ansgar W. Lohse

  6. Department of General and Visceral Surgery, Paracelsus Medical University/Salzburger Landeskliniken (SALK), Salzburg, Austria

    Klaus Emmanuel

  7. Department of General and Visceral Surgery, Krankenhaus Barmherzige Schwestern, Linz, Austria

    Klaus Emmanuel

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  1. Andrej Wagner
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Wagner, A., Kiesslich, T., Neureiter, D. et al. Photodynamic therapy for hilar bile duct cancer: clinical evidence for improved tumoricidal tissue penetration by temoporfin. Photochem Photobiol Sci 12, 1065–1073 (2013). https://doi.org/10.1039/c3pp25425a

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