A novel therapeutic technology called photochemical internalization combined with gemcitabine yielded promising safety and efficacy results in patients with inoperable perihilar cholangiocarcinoma (CCA), as published in The Oncologist.

Photochemical internalization utilizes a photosensitizing molecule, fimaporfin, to enhance the localized endosomal release of drugs, such as chemotherapy, to reach their therapeutic targets inside of the cell. Fimaporfin, once activated through targeted illumination of the lesion to be treated, disrupts the endosomal membranes inside of the targeted cells and allows for a greater therapeutic effect.

The results showed that disease control was achieved in 10 out of the 11 evaluable patients with 75% having progression-free survival at 6 months. The median overall survival was 15.4 months. In the highest fimaporfin dose group (n=6) the median overall survival was even higher at 22.8 months.


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The authors mention that these results are promising since the phase 3 ABC-02 trial which established gemcitabine plus cisplatin as the standard of care had a median overall survival of only 11.7 months. The current study also achieved a complete response in 2 of the 11 patients compared to only 1 patient in the ABC-02 study.

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“Photochemical internalization with gemcitabine was found to be safe and resulted in encouraging response and survival rates in patients with unresectable perihilar CCA,” the authors said.

No unexpected safety signals were observed during the study and the most common adverse event during the study was photosensitivity which occurred in 75% of the patients. The photosensitivity generally occurred within the first 30 days after treatment with fimaporfin and was mild in most cases with only 2 moderate blistering events recorded.

The most significant adverse event observed was cholangitis which occurred in 56% of patients. Cholangitis is common in patients receiving CCA treatment through biliary drainage and the rate was similar to that seen in patients receiving standard treatment, the authors said.

Patients in the study received intravenous fimaporfin at day 0 followed by an infusion of 1000 mg/m2 of gemcitabine along with intraluminal laser light illumination. Patients in the study were chosen as they had tumors that could be fully illuminated from inside of the bile duct. Between 7 and 21 days after illumination, patients began up to 8 cycles of the standard gemcitabine plus cisplatin (25 mg/m2) treatment.

Reference

Trojan J, Hoffmeister A, Neu B, et al. Photochemical internalization of gemcitabine is safe and effective in locally advanced inoperable cholangiocarcinoma. Oncologist. Published online March 7, 2022. doi:10.1093/oncolo/oyab074