Torisel: Temsirolimus recently approved by FDA as new molecular entity

Temsirolimus is now approved by FDA as an antineoplastic agent for the treatment of advanced renal cell carcinoma.

Key Points

New molecular entities

WYETHAntineoplastic agent approved for the treatment of advanced renal cell carcinoma
This agent is an mTOR inhibitor that binds to intracellular protein FKBP-12, inhibiting the activity of mTOR and thereby inhibiting cell growth and division. Temsirolimus was approved on May 30, 2007, for the treatment of advanced renal cell carcinoma.

Efficacy. The efficacy of temsirolimus was evaluated in a phase 3, multicenter, 3-arm, randomized, open-label study in previously untreated patients with advanced renal cell carcinoma (both clear cell and non-clear cell histologies). Patients were randomized 1:1:1 to receive either interferon alfa (n=207), temsirolimus 25 mg once weekly (n=209), or interferon alfa plus temsirolimus 15 mg (n=210). The intent-to-treat (ITT) population included 626 patients. The median duration of treatment among patients treated with temsirolimus alone was 17 weeks (range, 1–126 wk) compared with a median 8-week treatment duration among patients treated with interferon alfa alone (range, 1–124 wk). Patients treated with temsirolimus alone demonstrated a statistically significant (defined as P<.0159; O'Brien-Fleming boundary) improvement in overall survival (OS) (median OS, 10.9 mo; 95% CI, 8.6–12.7) compared with patients treated with interferon alfa alone (median OS, 7.3 mo; 95% CI, 6.1–8.8; P=.0078; HR=0.73; 95% CI, 0.58–0.92). Combination therapy did not result in a statistically significant improvement in OS when compared with interferon alfa monotherapy. Patients treated with temsirolimus alone also demonstrated statistically significant improvement in median progression-free survival (PFS) in blinded independent radiologic assessments of tumor response (median PFS, 5.5 mo; 95% CI, 3.9–7.0) versus patients treated with interferon alfa alone (median PFS, 3.1 mo; 95% CI, 2.2–3.8; P=.0001; HR=0.66; 95% CI, 0.53–0.81). Overall response rate (ORR) did not differ significantly between the temsirolimus monotherapy and interferon alfa monotherapy groups (temsirolimus monotherapy group ORR, 8.6%; 95% CI, 4.8%–12.4%; interferon alfa monotherapy group ORR, 4.8%; 95% CI, 1.9%–7.8%; P=.1232).

Dosing. A 25-mg dose of temsirolimus should be infused over a 30- to 60-minute period once weekly. Temsirolimus treatment should continue until disease progression or unacceptable toxicity occurs. Patients should also receive a prophylactic dose of intravenous diphenhydramine 25 to 50 mg (or similar antihistamine) approximately 30 minutes before each temsirolimus dosing period. If patients experience absolute neutrophil count <1,000/mm3, platelet count <75,000/mm3, or National Cancer Institute Common Terminology Criteria for Adverse Events ≥grade 3 adverse reactions, temsirolimus treatment should be discontinued until toxicities have resolved to ≤grade 2; when temsirolimus treatment is restarted, the dose should be reduced by 5 mg/wk (to a dose no lower than 15 mg/wk).