Journal article
A phase I study to determine the maximum tolerated dose and safety of oral LR-103 (1,24(S)Dihydroxyvitamin D-2) in patients with advanced cancer
Journal of oncology pharmacy practice, Vol.21(6), pp.416-424
12/01/2015
DOI: 10.1177/1078155214541572
PMCID: PMC4281509
PMID: 24986793
Abstract
Background The objective of this study was to determine the maximum tolerated dose and safety of LR-103, a Vitamin D analogue, in patients with advanced cancer.
Methods In Step A, patients received oral LR-103 once daily in 14-day cycles with intra-patient dose escalation per accelerated dose escalation design. Dose limiting toxicity for Step A was defined as grade 2 hypercalcemia and/or >grade 2 other toxicities. Starting dose was 5 mu g/day. Step B used a 3+3 design starting at Step A maximum tolerated dose with 28-day cycles. Dose limiting toxicity was defined as grade 3 hypercalcemia or any grade 3 or 4 non-hematologic toxicity, except hypercalciuria.
Results Twenty-one patients were enrolled; eight were treated in Step A. At dose level 3 (15 mu g/day), two patients had dose limiting toxicity. One had grade 4 hyperuricemia. The other had grade 4 GGT plus grade 3 alkaline phosphatase, fatigue and urinary tract infection (UTI). Dose level 2 (10 mu g/day) was the maximum tolerated dose for Step A and was starting dose for Step B. The dose was escalated to dose level 5 (30 mu g/day) with a patient experiencing grade 3 dose limiting toxicity of hypercalcemia. The study was discontinued before reaching the maximum tolerated dose due to sponsor decision. Modest increases in serum osteocalcin and calcium and decrease in parathyroid hormone were noted. Best response was stable disease; four patients were on therapy for six months or longer.
Conclusion Step A dose limiting toxicities limited accelerated dose escalation. The maximum tolerated dose of LR-103 was not reached prior to study termination and this agent is no longer being developed.
Details
- Title: Subtitle
- A phase I study to determine the maximum tolerated dose and safety of oral LR-103 (1,24(S)Dihydroxyvitamin D-2) in patients with advanced cancer
- Creators
- Kari B. Wisinski - University of Wisconsin Carbone Cancer CenterWendy M. Ledesma - University of Wisconsin Carbone Cancer CenterJill Kolesar - University of Wisconsin Carbone Cancer CenterGeorge Wilding - University of Wisconsin Carbone Cancer CenterGlenn Liu - University of Wisconsin Carbone Cancer CenterJeffrey Douglas - University of Illinois Urbana-ChampaignAnne M. Traynor - University of Wisconsin Carbone Cancer CenterMark Albertini - University of Wisconsin–MadisonDaniel Mulkerin - University of Wisconsin Carbone Cancer CenterHoward H. Bailey - University of Wisconsin Carbone Cancer Center
- Resource Type
- Journal article
- Publication Details
- Journal of oncology pharmacy practice, Vol.21(6), pp.416-424
- Publisher
- Sage
- DOI
- 10.1177/1078155214541572
- PMID
- 24986793
- PMCID
- PMC4281509
- ISSN
- 1078-1552
- eISSN
- 1477-092X
- Number of pages
- 9
- Grant note
- P30 CA014520; P30 CA14520 / NCI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) P30CA014520 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 12/01/2015
- Academic Unit
- Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984696542802771
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