Phase IIb Trial for the Palliative Treatment of Patients With Primary Hepatic Malignancy Unable to Receive Curative Treatment: Efficacy of Colchicine.

Abstract

This trial was to evaluate the efficacy and the safety of colchicine for the palliative treatment of patients with primary hepatic malignancy unable to receive curative treatment. Forty hepatocellular carcinoma (HCC) patients and two intrahepatic cholangiocarcinoma (ICC) patients signed the informed consents. Most HCC participants (97%) had failed in tyrosine kinase inhibitor (TKI) and/or immunotherapy before entering the study. Colchicine was started from 1 mg twice per day and was adjusted ranging from 1.5 to 3 mg/day. One treatment cycle was defined as four continuous treatment days followed by 3 days off. The HCC control group was matched to the same condition (Child score, tumor staging, previous TKI, and/or immunotherapy) as the participants at a ratio of 3 to 1 (control to colchicine). The ICC control group was matched to the same tumor staging as the participants. The primary objective was to compare the survival between the two groups. The safety objective was to observe the adverse events of colchicine. The colchicine HCC group demonstrated longer median survival (283 days) than the control group (107 days) (p < 0.0001, 95% confidence interval 2.001-3.289, hazard ratio 0.3513, 95% confidence interval 0.2611-0.5523). Two ICC participants survived 491 and 461 days, respectively, compared to the control group with a median survival of 8.5 months and a 41.5% one-year survival rate. Diarrhea (5%) was the only directly colchicine-related grade 3-4 adverse event. In conclusion, this colchicine dosage schedule is clinically feasible as an effective palliative treatment for patients with primary hepatic malignancy unable to receive curative treatment. Trial Registration: ClinicalTrials.gov identifier: NCT04264260.