Abstract
Photochemical 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 previously indicated by clinical data using
other localized treatment modalities, adding a directed, tumor-targeting treatment
to systemic therapy to ameliorate the progressively expanding extrahepatic tumor burden
can have important effects on the overall outcome of systemic treatment in many patients
who have incurable eCCA.
