A phase I/II pharmacokinetic and pharmacogenomic study of calcitriol in combination with cisplatin and docetaxel in advanced non-small-cell lung cancer

Background Preclinical studies demonstrated antiproliferative synergy of 1,25-D 3 (calcitriol) with cisplatin. The goals of this phase I/II study were to determine the recommended phase II dose (RP2D) of 1,25-D 3 with cisplatin and docetaxel and its efficacy in metastatic non-small-cell lung cancer. Methods Patients were ≥18 years, PS 0–1 with normal organ function. In the phase I portion, patients received escalating doses of 1,25-D 3 intravenously every 21 days prior to docetaxel 75 mg/m 2 and cisplatin 75 mg/m 2 using standard 3 + 3 design, targeting dose-limiting toxicity (DLT) rate T) correlated with disease progression ( P = 0.03) and CYP24A1 SNP rs2762939 (C > G) trended toward PR/SD ( P = 0.08). There was no association between 1,25-D 3 PK and CYP24A1 SNPs. Conclusions The RP2D of 1,25-D 3 with docetaxel and cisplatin was 60 mcg/m 2 every 21 days. Pre-specified endpoint of 50 % confirmed RR was not met in the phase II study. Functional SNPs in CYP24A1 may inform future studies individualizing 1,25-D 3 .