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FDA Approval for Temsirolimus

Brand name: Toriselâ„¢

  • Approved for kidney cancer

Full prescribing information is available, including clinical trial information, safety, dosing, drug-drug interactions and contraindications.

On May 30, 2007, the U. S. Food and Drug Administration granted approval for temsirolimus (Toriselâ„¢, made by Wyeth, Inc.) for the treatment of advanced renal cell carcinoma (RCC).

Efficacy and safety were demonstrated at a second interim analysis of a phase 3, multicenter, international, randomized, open-label study in previously untreated patients with advanced RCC who had 3 or more of 6 poor prognostic factors. These factors included time from diagnosis to randomization of less than one year, Karnofsky performance status of 60 or 70, blood hemoglobin level less than the lower limit of normal, corrected serum calcium level of greater than 10 mg/dL, serum lactate dehydrogenase level 1.5 times the upper limit of normal, and/or more than one metastatic organ site.

Six hundred and twenty six patients were randomly assigned to one of three arms: Interferon alfa (IFN) alone (n=207), temsirolimus 25 mg alone (n=209), or the combination of temsirolimus (15 mg) and IFN (n=210). Patients were stratified for prior nephrectomy and geographic region. Seventy percent were less than 65 years of age and 69 percent were male. Temsirolimus was infused intravenously over 30-60 minutes once a week until either disease progression or unacceptable toxicity. Premedication with an antihistamine (e.g., diphenhydramine) was recommended (see the protocol summary).

Single-agent temsirolimus was associated with a statistically significant improvement in overall survival (OS) when compared to IFN (hazard ratio 0.73 [95% CI: 0.58, 0.92]; p= 0.0078). The median OS was 10.9 months on the temsirolimus arm and 7.3 months on the IFN arm. Progression-free survival (PFS) was a secondary endpoint and the median PFS was 5.5 months on the temsirolimus arm and 3.1 months on the IFN arm [hazard ratio 0.66 (95% CI: 0.53, 0.81)]. The combination of 15 mg temsirolimus and IFN did not result in a significant increase in OS when compared with IFN alone and was associated with an increase in multiple adverse reactions.

The most common adverse reactions that occurred with a frequency greater than 30 percent were rash, asthenia, mucositis, nausea, edema, and anorexia. The most common laboratory abnormalities that occurred with a frequency of greater than 30 percent were anemia, hyperglycemia, hyperlipemia, hypertriglyceridemia, elevated serum alkaline phosphatase, elevated serum creatinine, lymphopenia, hypophosphatemia, thrombocytopenia, elevated serum aspartate transaminase (AST), and leukopenia.

Severe adverse reactions (grade 3 or 4) included asthenia, dyspnea, rash, and pain. Rare serious adverse reactions associated with temsirolimus included interstitial lung disease, bowel perforation, and acute renal failure. Severe laboratory abnormalities (grade 3 or 4) included hypertriglyceridemia, anemia, hypophosphatemia, hyperglycemia, lymphopenia, and neutropenia.

This summary was provided by Richard Pazdur, M.D., director of the FDA's Division of Oncology Drug Products.

The FDA is the division of the U.S. Department of Health and Human Services charged with ensuring the safety and effectiveness of new drugs and other products. (See "Learn How Drugs and Devices Get Approved.") The FDA's mission is to promote and protect the public health by helping safe and effective products to reach the market in a timely way, and monitoring products for continued safety after they are in use.

  • Updated: July 3, 2013