Phase I, pharmacokinetic study of temsirolimus administered orally to patients with advanced cancer

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.