The concomitant use of drug-eluting bead, irinotecan therapy (DEBIRI), and chemotherapy with gemcitabine/cisplatin may increase survival in patients with unresectable intrahepatic cholangiocarcinoma (CCA), according to results of a multicenter, randomized phase 2 clinical trial.
Although the preferred approach to CCA is surgical resection, most patients are not eligible for surgery due to advanced disease progression. Currently, the standard of care for these patients consists of gemcitabine/cisplatin chemotherapy with a mean overall survival (OS) of less than 12 months.
DEBIRI is a hepatic-directed therapy administrated through an arterial puncture and distributed in a lobar manner depending on tumor distribution. The number of treatments is decided based on factors such as treatment response and patient tolerance.
In previous studies, the authors demonstrated the effectiveness and safety of DEBIRI in combination with other drug regimes for intrahepatic CCA. Nonetheless, this is the first clinical trial that combines DEBIRI with the frontline chemotherapy for unresectable intrahepatic CCA.
The clinical trial included 46 adult patients with histologically proven unresectable intrahepatic CCA. Participants had more than 80% tumor body burden confined to the liver but less than 60% of hepatic compromise.
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Patients were randomized into 2 groups, one receiving gemcitabine/cisplatin alone and the other receiving combination therapy. Both groups had similar disease extension, target lesions (lesions bigger than 1 cm), and comorbidities. Response to treatment was evaluated through Response Evaluation Criteria in Solid Tumors (RESIST) and modified RESIST.
The results showed a better response to treatment in patients who received combined therapy, with a treatment response rate of over 80% in the first 2 months compared to under 60% in the control group; similar results were observed in months 4 and 6. The P-value was under 0.005 in all 6 months of treatment.
Tumor downsizing into resection/ablation was also more frequent in the combined therapy group (25% compared to 8%). Survival clearly improved in the combined therapy group with a mean progression-free disease survival of over 30 months compared to the approximately 10 months of the control group. OS in the combined therapy group was 33 months compared to the 12 months of the control group.
The authors did not report a significant increase in either adverse effects or in chemotherapy-associated adverse events.
“These results in the [gemcitabine/cisplatin]-DEBIRI arm, compared with previous published studies using conventional chemoembolization, demonstrates a significant improvement in response rate, progression-free survival, and overall survival,” the authors concluded.
Martin RC, Simo KA, Hansen P, et al. Drug-eluting bead, irinotecan therapy of unresectable intrahepatic cholangiocarcinoma (Deltic) with concomitant systemic gemcitabine and cisplatin. Ann Sur Oncol. Published online June 3, 2022. doi:10.1245/s10434-022-11932-3