Temsirolimus (Torisel, Wyeth), the first mTOR (mammalian target of rapamycin) inhibitor, was recently approved for the treatment
of advanced renal cell carcinoma (RCC). "Torisel provides a new option for physicians for the treatment of renal cell carcinoma,"
said Cindy O'Bryant, Pharm.D., BCOP, assistant professor at the University of Colorado Health Sciences Center School of Pharmacy,
Denver.
"Torisel shows promise in treating RCC—a hard tumor to treat," added James Trovato, Pharm.D., MBA, BCOP, associate professor
of pharmacy practice at the University of Maryland School of Pharmacy. "It will probably be used as a first-line agent for
patients with poor prognostic factors such as advanced or metastatic disease."
The American Cancer Society estimates that more than 50,000 new cases of RCC will be diagnosed in 2007 and more than 40% of
the patients will be diagnosed with advanced disease.
The safety and efficacy of temsirolimus were studied in a randomized, open-label, multicenter, phase III study in 626 previously
untreated patients with advanced RCC and with three or more of six prespecified prognostic factors. Patients were randomly
assigned to receive alpha interferon 3 million units subcutaneously three times a week, with an increase up to 18 million
units; temsirolimus 25 mg IV weekly; or combination therapy with temsirolimus 15 mg IV weekly and alpha interferon 6 million
units three times weekly. The results showed that temsirolimus significantly improved median overall survival, the primary endpoint, compared with alpha
interferon. The combination group did not show a significant increase in overall survival compared with the alpha interferon
group. Temsirolimus also demonstrated a significant benefit in median progression-free survival, a secondary endpoint, compared
with alpha interferon.
According to the product labeling, the most common adverse reactions observed with temsirolimus are rash, asthenia, mucositis,
nausea, edema, and anorexia. Hypersensitivity reactions have been observed with temsirolimus. "With alpha interferon, we see
many intolerant side effects; with Torisel, we see fewer," said O'Bryant.
In the phase III clinical trial, grade 3 or 4 adverse events occurred in 67% of the patients in the temsirolimus group compared
with 78% of the patients in the alpha-interferon group. The manufacturer recommends monitoring patients for the occurrence
of infections, including opportunistic infections, because temsirolimus may cause immunosuppression.
Pharmacokinetic studies show that strong inducers and inhibitors of CYP3A4 may affect concentrations of temsirolimus' primary
metabolite. According to Wyeth, if alternatives can't be used, a dose reduction to 12.5 mg/week should be considered when
used with strong CYP3A4 inhibitors and a dose increase from 25 mg/week up to 50 mg/week should be considered when used with
strong inducers of CYP3A4.
The recommended dose of temsirolimus for advanced RCC is 25 mg infused over a 30- to 60-minute period once a week. Treatment
should continue until disease progression or unacceptable toxicity occurs.
Temsirolimus must be stored under refrigeration and protected from light. According to the labeling, the vial contents must
first be diluted with the enclosed diluent before diluting the resultant solution with 250 ml of 0.9% sodium chloride solution
in non-DEHP containers and administered through polyethylene-lined administration sets. The stability of temsirolimus in other
solutions has not been studied.
TIPS TO REMEMBER ....Torisel
- Live vaccinations and close contact with people who have received live vaccines should be avoided.
- Torisel is classified as Pregnancy Category D. Women of childbearing potential should be advised to avoid becoming pregnant
throughout treatment and for three months after Torisel therapy has stopped.
- Premedication with 25-50 mg diphenhydramine IV should be given 30 minutes prior to each dose of Torisel.
THE AUTHOR is a writer based in New Jersey.
