Hudes G et al. (2007) Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 356: 2271–2281

Interferon (IFN)-α is a widely used agent for the treatment of metastatic renal cell carcinoma (RCC), but it has limited efficacy and considerable toxicity. Temsirolimus, an inhibitor of mammalian target of rapamycin kinase, has anti-proliferative and anti-angiogenic properties. Encouraging results were seen in phase I and II studies of temsirolimus in patients with metastatic RCC, a tumor characterized by unregulated angiogenesis. Hudes et al., therefore, conducted a multicenter, phase III trial that compared IFN-α alone with either temsirolimus alone or IFN-α plus temsirolimus for the treatment of patients with newly diagnosed metastatic RCC.

Patients (n = 626) with poor-prognosis metastatic RCC who had not previously received systemic treatment were randomly assigned to IFN-α alone (3 million U subcutaneously three times weekly in week 1, increasing to 18 million U three times weekly by week 3 if tolerated), temsirolimus alone (25 mg once-weekly by intravenous infusion), or IFN-α (6 million U subcutaneously three times weekly) plus temsirolimus (15 mg once-weekly).

Patients treated with temsirolimus alone had significantly improved overall survival compared with patients who received IFN-α alone (hazard ratio for death 0.73, 95% CI 0.58–0.92; P = 0.008). Combination therapy did not result in significantly better overall survival than that achieved with IFN-α alone. The temsirolimus-alone group had fewer serious adverse effects than the IFN-α group, although some less serious adverse effects, such as hyperglycemia and hyperlipidemia, were more common in the temsirolimus group.

Compared with IFN-α alone, temsirolimus moderately improved overall survival in patients with very advanced RCC and might, therefore, also benefit patients with less advanced disease.