A phase I study of the vitamin D3 analogue ILX23-7553 administered orally to patients with advanced solid tumors.
Invest New Drugs
; 29(6): 1420-5, 2011 Dec.
Article
en En
| MEDLINE
| ID: mdl-20661623
ABSTRACT
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 ANDMETHODS:
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 µg/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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Colecalciferol
/
Neoplasias
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Antineoplásicos
Límite:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Invest New Drugs
Año:
2011
Tipo del documento:
Article
País de afiliación:
Estados Unidos