Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Torisel (Wyeth)
vials containing 25 mg/mL concentrate
Approved indication: advanced renal cell carcinoma
Australian Medicines Handbook section 14.2.3

About 30% of patients with renal cell carcinoma have advanced or metastatic disease at the time of diagnosis. Chemotherapy is generally ineffective and nephrectomy is the mainstay of treatment for disease confined to the kidney. Treatment with drugs such as interferon alfa, interleukin-2 and the tyrosine kinase inhibitors sunitinib and sorafenib may benefit some patients.1

Temsirolimus is a kinase inhibitor derived from sirolimus (rapamycin) (see Aust Prescr 2002;25:97-9). It works by inhibiting the action of an enzyme called 'mammalian target of rapamycin' or mTOR. Inhibition prevents the division of cancerous cells, slowing the growth and spread of the cancer.

Following intravenous administration, temsirolimus is extensively metabolised by CYP3A4, with the main metabolite being sirolimus. The half-life is 17 hours for temsirolimus and 55 hours for sirolimus. Metabolites are primarily eliminated in the faeces.

The efficacy of temsirolimus in advanced renal cell carcinoma was first assessed in a dose escalation trial of 111 previously treated patients. After a weekly dose of 25, 75 or 250 mg (for a median of 5.6 months), 7% of the patients had a complete or partial response to temsirolimus, but this was not dose-dependent.2In a larger trial of 626 previously untreated patients, median overall survival was longer in patients treated with temsirolimus (25 mg each week) than those treated with interferon alfa (10.9 months vs 7.3 months). Adding interferon alfa to temsirolimus did not improve the overall survival time and was associated with more serious adverse events than temsirolimus alone.3

In the trials, rash, fatigue, mucositis, nausea, oedema, anaemia and anorexia were common adverse events in patients receiving temsirolimus. The most frequent laboratory test abnormalities were hyperglycaemia, hypercholesterolaemia, hyperlipidaemia, hypophosphataemia, thrombocytopenia, leucopenia and elevated alkaline phosphatase, serum creatinine and aspartate aminotransferase.2,3

Approximately 5% of the participants in the larger trial had a hypersensitivity reaction to temsirolimus so patients should be given intravenous antihistamine approximately 30 minutes before temsirolimus is administered. If a hypersensitivity reaction develops, the temsirolimus infusion should be stopped.

Cases of interstitial lung disease have occurred in patients taking temsirolimus and patients should be advised to seek medical attention if they develop worsening respiratory symptoms. Other rare but serious adverse events that have been reported include fatal bowel perforation and renal failure. Patients with central nervous system tumours and/or taking anticoagulants may have an increased risk of intracerebral bleeding.

Immunosuppression may occur with temsirolimus, so be vigilant for infections. Also, live vaccines and contact with people who have recently had them should be avoided. Temsirolimus may delay wound healing and should not be given to patients in the peri-surgical period.

Drugs that induce or inhibit the CYP3A4 enzyme should be avoided in patients taking temsirolimus. Concomitant use of sunitinib can result in dose-limiting toxicities such as serious maculopapular rash and gout or cellulitis requiring hospitalisation. Angioneurotic oedema-type reactions have been observed in patients who were receiving temsirolimus concomitantly with an angiotensin converting enzyme inhibitor. Some patients on temsirolimus and interferon alfa have developed cataracts.

Temsirolimus provides another option for patients with advanced renal cell carcinoma. However, its relative efficacy compared to tyrosine kinase inhibitors is not known.

Read about The Transparency Score Manufacturer provided the clinical evaluation

The Transparency Score ( ) is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.

Notes on references

At the time the comment was prepared, information about this drug was available on the web site of the Food and Drug Administration in the USA (

At the time the comment was prepared, a scientific discussion about this drug was available on the website of the European Medicines Agency (