Abstract
Evaluation of: Cohen EE, Wu K, Hartford C et al. Phase I studies of sirolimus alone or in combination with pharmacokinetic modulators in advanced cancer patients. Clin. Cancer. Res. 18(17), 4785–4793 (2012).The mTOR pathway mediates many biologic functions such as transcriptional and translational control, and is a target for anticancer drug development. mTOR inhibitors, such as sirolimus (SRL), display immunosuppressive and antiproliferative properties, and the use of SRL in kidney transplant recipients reduces the risk of post-transplant cancer. However, its use in advanced cancer patients has not been fully evaluated. The authors review the study by Cohen et al., evaluating the dose for oral, weekly SRL alone or in combination with grapefruit juice or ketoconazole to achieve the desired whole-blood concentration with antitumoral activity. This study demonstrates that SRL can be feasibly administered orally once weekly and displays a similar pharmacokinetic profile compared with other mTOR inhibitors. This study encouraged the use of SRL in advanced cancer patients and can stimulate clinical trials with a larger number of patients, evaluating the role of SRL as a new targeted therapy in cancer patients.
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