Evaluation of Efficacy, Safety and Tolerability of High Dose-Intermittent Calcitriol Supplementation to Advanced Intrahepatic Cholangiocarcinoma Patients - A Pilot Study

Antitumor activity (growth suppression) of vitamin D has been demonstrated using cholangiocarcinoma(CCA) cell lines, CCA cell-grafted animal models, and human CCA tissue cultures. The present study aimed todetermine the toxicity and tolerability of intermittent-high dose calcitriol in advanced inoperable intrahepaticCCA patients and to evaluate the therapeutic efficacy of combinations of calcitriol and 5-fluorouracil-basedchemotherapeutic drugs. The patients were divided into 3 groups: the first (n=2) received intermittent-highdose oral calcitriol 12 μg/day for 3 days, i.e. Monday-Wednesday, per week up to 3 months. The treatment didnot cause any serious adverse events, except hypercalcemia grade I, once in 72 administrations. The secondgroup (n=3) received chemotherapeutic drugs (5-fluorouracil, Mitomycin C and Leucovorin) for 3 cycles, onepatient showing a partial response. The third group (n=4) received high dose calcitriol in combination withchemotherapeutic-drugs. All 4 patients encountered serious adverse events and two of them were withdrawnafter the first drug cycle. This pilot study suggests that, although high dose-intermittent calcitriol appeared tobe safe and tolerated well in advanced intrahepatic CCA patients, co-administration with 5-fluorouracil-basedchemotherapeutic drugs caused unexpected potentiation of their toxicity. Adjustment of the doses of both drugs isrequired to avoid such toxicity and to optimize therapeutic efficacy of anticancer drugs when they were combinedwith high dose-intermittent calcitriol. USA Clinical Trial : NCT01039181.