Phase I, pharmacokinetic study of temsirolimus administered orally to patients with advanced cancer
- 5 May 2009
- journal article
- Published by Springer Science and Business Media LLC in Investigational New Drugs
- Vol. 28 (3), 334-342
- https://doi.org/10.1007/s10637-009-9257-1
Abstract
An oral formulation of temsirolimus (Torisel®), an inhibitor of the mammalian target of rapamycin, was evaluated on an intermittent schedule (once daily for 5 days every 2 weeks) in patients with advanced cancer. The maximum tolerated dose was determined to be 75 mg after dose-limiting toxicities of grade 3 elevated aminotransferases (1 patient) and grade 3 rash (1 patient) occurred with a 100-mg dose. The most common temsirolimus-related adverse events were mucositis, rash/maculopapular rash, and asthenia. Six of 12 patients who received the 75-mg dose required dose reductions due to temsirolimus-related adverse events. Two patients who received 75-mg temsirolimus and did not have dose reductions had minor tumor responses. Relative exposure from contributions of both temsirolimus and sirolimus, the principal metabolite, was 17.9% of the 75-mg dose. Thus, oral temsirolimus, 75 mg administered once daily for 5 days every 2 weeks, was further evaluated in patients with metastatic breast cancer.Keywords
This publication has 27 references indexed in Scilit:
- Phase II Study of Erlotinib in Recurrent or Metastatic Endometrial Cancer: NCIC IND-148Journal of Clinical Oncology, 2008
- Low‐dose, single‐agent temsirolimus for relapsed mantle cell lymphomaCancer, 2008
- A Phase I and Pharmacokinetic Study of Temsirolimus (CCI-779) Administered Intravenously Daily for 5 Days Every 2 Weeks to Patients with Advanced CancerClinical Cancer Research, 2006
- Antiangiogenic Potential of the Mammalian Target of Rapamycin Inhibitor TemsirolimusCancer Research, 2006
- CCI-779 Inhibits Rhabdomyosarcoma Xenograft Growth by an Antiangiogenic Mechanism Linked to the Targeting of mTOR/Hif-1α/VEGF SignalingNeoplasia, 2006
- Hypoxia-inducible factor determines sensitivity to inhibitors of mTOR in kidney cancerNature Medicine, 2005
- Phase II Trial of Single-Agent Temsirolimus (CCI-779) for Relapsed Mantle Cell LymphomaJournal of Clinical Oncology, 2005
- Safety and Pharmacokinetics of Escalated Doses of Weekly Intravenous Infusion of CCI-779, a Novel mTOR Inhibitor, in Patients With CancerJournal of Clinical Oncology, 2004
- Randomized Phase II Study of Multiple Dose Levels of CCI-779, a Novel Mammalian Target of Rapamycin Kinase Inhibitor, in Patients With Advanced Refractory Renal Cell CarcinomaJournal of Clinical Oncology, 2004
- Combining the Anti-EGFR Agent Gefitinib With Chemotherapy in Non–Small-Cell Lung Cancer: How Do We Go From INTACT to Impact?Journal of Clinical Oncology, 2004