Photochemical internalization and gemcitabine combined with first-line chemotherapy in perihilar cholangiocarcinoma: observations in three patients

Endosc Int Open 2020; 08: E1878-E1883 DOI: 10.1055/a-1276-6366Photochemical internalization (PCI) is a technology to induce a localized, intracellular enhancement of therapeutics that are processed through endosomal pathways, including gemcitabine in malignant cells. In addition to a direct phototoxic and tumoricidal effect, PCI specifically disrupts endosomal membranes and, thereby, the compartmentalization of certain cytotoxic compounds to enhance a drug’s intended intracellular target reach within the tissue treated.Non-resectable extrahepatic cholangiocarcinoma (eCCA) is a common primary tumor and gemcitabine/cisplatin chemotherapy is widely considered standard of care for it. PCI is well suited as an endoscopic intervention, and clinical observations in three subjects participating in a phase I/IIa dose escalation safety trial are described. The trial included patients with perihilar, non-resectable CCA suitable for standard-of-care chemotherapy. Per protocol, a single endoscopic PCI procedure with gemcitabine was conducted at the initiation of standard gemcitabine/cisplatin therapy. Sixteen patients enrolled in the initial dose escalation phase of the trial, which later was extended to explore the safety of a second PCI procedure during chemotherapy.While limited to a case series, the various clinical observations described here serve to illustrate the effects of localized, perihilar tumor targeting in appropriate patients by any safe methodology, including PCI. As pr...
Source: Endoscopy International Open - Category: Gastroenterology Authors: Tags: Innovation forum Source Type: research