Phase I studies of sirolimus alone or in combination with pharmacokinetic modulators in advanced cancer patients.

ABSTRACT:

Purpose

Sirolimus is the eponymous inhibitor of the mTOR; however, only its analogs have been approved as cancer therapies. Nevertheless, sirolimus is readily available, has been well studied in organ transplant patients, and shows efficacy in several preclinical cancer models.

Experimental design

Three simultaneously conducted phase I studies in advanced cancer patients used an adaptive escalation design to find the dose of oral, weekly sirolimus alone or in combination with either ketoconazole or grapefruit juice that achieves similar blood concentrations as its intravenously administered and approved prodrug, temsirolimus. In addition, the effect of sirolimus on inhibition of p70S6 kinase phosphorylation in peripheral T cells was determined.

Results

Collectively, t

SUBMITTER: Cohen EE 

PROVIDER: S-EPMC4410974 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature