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 to determine the toxicity and tolerability of intermittent-high dose calcitriol in advanced inoperable intrahepatic CCA patients and to evaluate the therapeutic efficacy of combinations of calcitriol and 5-fluorouracil-based chemotherapeutic drugs. The patients were divided into 3 groups: the first (n=2) received intermittent-high dose oral calcitriol 12 μg/day for 3 days, i.e. Monday-Wednesday, per week up to 3 months. The treatment did not cause any serious adverse events, except hypercalcemia grade I, once in 72 administrations. The second group (n=3) received chemotherapeutic drugs (5-fluorouracil, Mitomycin C and Leucovorin) for 3 cycles, one patient showing a partial response. The third group (n=4) received high dose calcitriol in combination with chemotherapeutic-drugs. All 4 patients encountered serious adverse events and two of them were withdrawn after the first drug cycle. This pilot study suggests that, although high dose-intermittent calcitriol appeared to be safe and tolerated well in advanced intrahepatic CCA patients, co-administration with 5-fluorouracil-based chemotherapeutic drugs caused unexpected potentiation of their toxicity. Adjustment of the doses of both drugs is required to avoid such toxicity and to optimize therapeutic efficacy of anticancer drugs when they were combined with high dose-intermittent calcitriol.