A phase I study of the vitamin D(3) analogue ILX23-7553 administered orally to patients with advanced solid tumors.
Summary of "A phase I study of the vitamin D(3) analogue ILX23-7553 administered orally to patients with advanced solid tumors."
Purpose ILX23-7553 (1,25-dihydroxy-16-ene-23-yne vitamin D3) is a vitamin D analogue that was developed to avoid the hypercalcemia that may limit the use of vitamin D as an anti-cancer agent. We performed a phase I study of ILX23-7553 to determine its side-effect profile, pharmacokinetics, and to document any observed antitumor activity. Patients and Methods Adult patients with refractory solid tumors were enrolled. A modified Fibonacci dose escalation scheme was employed. ILX23-7553 was administered orally daily for three consecutive days, and repeated in 7-day cycles. Plasma drug concentrations were assayed by radioimmunoassay and radioreceptor assay. Results Sixteen patients were enrolled to 10 dose levels ranging from 1.7 to 37.3 mug/m(2)/day. The maximum tested dose was six times higher than the maximally-tolerated dose (MTD) in dogs. Dose-limiting toxicity was not observed. ILX23-7553 concentrations on cycle 1 day 1 of treatment were comparable to concentrations on cycle 2 day 1, suggesting limited accumulation. One patient with adrenal cortical cancer had stable disease for 23 weeks, but no objective responses were observed. Conclusions ILX23-7553 was well tolerated at the doses tested, with no evidence of hypercalcemia. The plasma concentrations achieved were approximately 100-fold lower than those associated with tumor growth inhibition in vitro, limiting use of this formulation.
The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
This article was published in the following journal.
Name: Investigational new drugs
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20661623
- DOI: http://dx.doi.org/10.1007/s10637-010-9492-5
Medical and Biotech [MESH] Definitions
A lipid cofactor that is required for normal blood clotting. Several forms of vitamin K have been identified: VITAMIN K 1 (phytomenadione) derived from plants, VITAMIN K 2 (menaquinone) from bacteria, and synthetic naphthoquinone provitamins, VITAMIN K 3 (menadione). Vitamin K 3 provitamins, after being alkylated in vivo, exhibit the antifibrinolytic activity of vitamin K. Green leafy vegetables, liver, cheese, butter, and egg yolk are good sources of vitamin K.
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