A phase I study of the vitamin D3 analogue ILX23-7553 administered orally to patients with advanced solid tumors.
OBJECTIVE
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.


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 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.
Jain
Rajul K
RK
The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Trump
Donald L
DL
Egorin
Merrill J
MJ
Fernandez
Manuel
M
Johnson
Candace S
CS
Ramanathan
Ramesh K
RK
D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D002762:Cholecalciferol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011863:Radioimmunoassay; D011869:Radioligand Assay; D016896:Treatment Outcome
D000970:Antineoplastic Agents; C428283:ILX237553; D002762:Cholecalciferol