Phase I safety and pharmacodynamic of inecalcitol, a novel VDR agonist with docetaxel in metastatic castration-resistant prostate cancer patients.

Details

Serval ID
serval:BIB_E47375BB3E89
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Phase I safety and pharmacodynamic of inecalcitol, a novel VDR agonist with docetaxel in metastatic castration-resistant prostate cancer patients.
Journal
Clinical Cancer Research
Author(s)
Medioni J., Deplanque G., Ferrero J.M., Maurina T., Rodier J.M., Raymond E., Allyon J., Maruani G., Houillier P., Mackenzie S., Renaux S., Dufour-Lamartinie J.F., Elaidi R., Lerest C., Oudard S.
ISSN
1078-0432 (Print)
ISSN-L
1078-0432
Publication state
Published
Issued date
2014
Volume
20
Number
17
Pages
4471-4477
Language
english
Notes
Publication types: Journal ArticlePublication Status: ppublish
Abstract
PURPOSE: We conducted a phase I multicenter trial in naïve metastatic castrate-resistant prostate cancer patients with escalating inecalcitol dosages, combined with docetaxel-based chemotherapy. Inecalcitol is a novel vitamin D receptor agonist with higher antiproliferative effects and a 100-fold lower hypercalcemic activity than calcitriol.
EXPERIMENTAL DESIGN: Safety and efficacy were evaluated in groups of three to six patients receiving inecalcitol during a 21-day cycle in combination with docetaxel (75 mg/m2 every 3 weeks) and oral prednisone (5 mg twice a day) up to six cycles. Primary endpoint was dose-limiting toxicity (DLT) defined as grade 3 hypercalcemia within the first cycle. Efficacy endpoint was ≥30% PSA decline within 3 months.
RESULTS: Eight dose levels (40-8,000 μg) were evaluated in 54 patients. DLT occurred in two of four patients receiving 8,000 μg/day after one and two weeks of inecalcitol. Calcemia normalized a few days after interruption of inecalcitol. Two other patients reached grade 2, and the dose level was reduced to 4,000 μg. After dose reduction, calcemia remained within normal range and grade 1 hypercalcemia. The maximum tolerated dose was 4,000 μg daily. Respectively, 85% and 76% of the patients had ≥30% PSA decline within 3 months and ≥50% PSA decline at any time during the study. Median time to PSA progression was 169 days.
CONCLUSION: High antiproliferative daily inecalcitol dose has been safely used in combination with docetaxel and shows encouraging PSA response (≥30% PSA response: 85%; ≥50% PSA response: 76%). A randomized phase II study is planned.
Pubmed
Web of science
Open Access
Yes
Create date
11/02/2015 12:06
Last modification date
20/08/2019 16:08
Usage data