Temsirolimus: new drug. Metastatic kidney cancer: more assessment needed.

(1) Most kidney tumours are discovered at an advanced stage or after they have already metastasised. Even in these cases, surgical excision, when feasible, remains the first-line treatment. Chemotherapy only increases survival time by a few months, at a cost of frequent adverse effects. The best-assessed drug in this setting is interferon alfa; (2) Temsirolimus is marketed for first-line treatment of advanced-stage kidney cancer in patients who have risk factors associated with a poor prognosis. Temsirolimus is a water-soluble derivative of sirolimus. After intravenous administration it is rapidly metabolised into sirolimus; (3) Clinical evaluation is based on a randomised unblinded trial in 626 patients with kidney cancer. Nearly all of the patients had metastases, and all had at least 3 of the 6 risk factors associated with poor outcome. The median survival time was significantly longer with temsirolimus monotherapy than with interferon alfa-2a monotherapy (10.9 versus 7.3 months), but it was not longer with interferon alfa-2a + temsirolimus than with interferon alfa-2a alone; (4) There were fewer severe adverse events with temsirolimus than with interferon alfa-2a (66.8% versus 77.5% of patients, respectively). Yet temsirolimus provokes several serious adverse effects, such as hyperglycaemia, hypophosphataemia, and hypokalaemia. Other adverse effects include hypersensitivity reactions, bleeding and infections; (5) Temsirolimus is metabolised by cytochrome P450 isoenzyme CYP 3A4, creating a risk of pharmacokinetic interactions; (6) In practice, the only evidence supporting the efficacy of temsirolimus is based on a single unblinded trial. Adverse effects are frequent and sometimes serious. Additional comparative trials are needed.