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

TY - JOUR

T1 - Photodynamic therapy for hilar bile duct cancer: clinical evidence for improved tumoricidal tissue penetration by temoporfin

AU - Wagner, Andrej

AU - Kiesslich, Tobias

AU - Neureiter, Daniel

AU - Friesenbichler, Paul

AU - Puespoek, Andreas

AU - Denzer, Ulrike W

AU - Wolkersdörfer, Gernot W

AU - Emmanuel, Klaus

AU - Lohse, Ansgar W

AU - Berr, Frieder

PY - 2013/6/1

Y1 - 2013/6/1

N2 - 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.

AB - 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.

KW - Aged

KW - Aged, 80 and over

KW - Antineoplastic Agents

KW - Bile Duct Neoplasms

KW - Bile Ducts

KW - Female

KW - Humans

KW - Male

KW - Mesoporphyrins

KW - Middle Aged

KW - Photochemotherapy

KW - Photosensitizing Agents

U2 - 10.1039/c3pp25425a

DO - 10.1039/c3pp25425a

M3 - SCORING: Journal article

C2 - 23558738

VL - 12

SP - 1065

EP - 1073

JO - PHOTOCH PHOTOBIO SCI

JF - PHOTOCH PHOTOBIO SCI

SN - 1474-905X

IS - 6

ER -