Wyeth Pharmaceuticals, a division of Wyeth, said its Torisel (temsirolimus) received the European Commission approval for the first-line treatment of patients with advanced renal cell carcinoma (RCC) who have at least three of six prognostic risk factors.

Torisel, approved in the US in May 2007 for the treatment of advanced RCC, is the only approved cancer therapy that specifically inhibits the mTOR (mammalian target of rapamycin) kinase, an important regulator of cell proliferation, cell growth and cell survival. Torisel was.

Renal cell carcinoma accounts for approximately 85 per cent of the estimated 85,000 new cases of kidney cancer diagnosed in Europe annually. Torisel is the only renal cancer therapy proved to extend median overall survival compared with interferon-alpha in patients with advanced RCC.

"Temsirolimus was studied in the most difficult-to-treat patients with advanced renal cell carcinoma: those who have multiple risk factors that have been associated with shortened survival," said Bernard Escudier, M.D., Head of the Immunotherapy Unit, Department of Medical Oncology, Institute Gustave Roussy, Villejuif, France, and an investigator in the Torisel phase III study. "The ability of temsirolimus to provide an increase in overall survival in these patients provides us with a much-needed new option for the treatment of advanced kidney cancer."

Torisel was studied in a three-arm, phase III clinical trial of 626 patients with advanced RCC and three or more of six reselected prognostic risk factors who had received no prior systemic therapy. In the study, Torisel significantly increased median overall survival by 49 percent compared with interferon-alpha (10.9 months vs. 7.3 months, P=0.0078). Torisel also was associated with a statistically significant improvement over interferon-alpha in the secondary endpoint of progression-free survival (when the disease does not worsen; 5.6 months vs. 3.2 months, P=0.0042). The combination of Torisel and interferon-alpha did not result in a significant increase in overall survival when compared with interferon-alpha alone.

"The European Commission's approval of Torisel underscores the importance of this therapy for patients with advanced kidney cancer and reinforces the potential of this mechanism of action as a new approach in oncology," said Robert R. Ruffolo, Jr., Ph.D., president, Wyeth Research, and senior vice president, Wyeth.

Torisel is an mTOR inhibitor indicated in the European Union for the first-line treatment of patients with advanced RCC who have at least three of six prognostic risk factors. These risk factors include less than one year from time of initial RCC diagnosis to randomisation, Karnofsky performance status of 60 or 70, haemoglobin less than the lower limit of normal, corrected calcium of greater than 10 mg/dL, lactate dehydrogenase >1.5 times the upper limit of normal and more than one metastatic organ site. In the United States, Torisel is indicated for the treatment of advanced RCC.

Inhibition of mTOR in treated cancer cells blocked the translation of genes that regulate the cell cycle. In in vitro studies using renal cancer cell lines, Torisel inhibited the activity of mTOR and resulted in reduced levels of certain cell growth factors involved in the development of new blood vessels, such as vascular endothelial growth factor.

In March 2007, the European Association of Urology published guidelines recommending that Torisel be considered as first-line treatment in patients with advanced RCC with poor-risk features. In August 2007, the National Comprehensive Cancer Network (NCCN) in the United States added Torisel to the NCCN Kidney Cancer Guidelines as an option in first-line therapy for both predominant clear cell histology and non-clear cell histology and as a subsequent therapy option for patients with predominant clear cell histology.

The use of Torisel is likely to result in hyperglycaemia, immunosuppression and hyperlipemia. This may result in the need for an increase in the dose of, or initiation of, insulin and/or oral hypoglycemic agent therapy and/or lipid-lowering agents, respectively.

Patients with central nervous system tumours (primary CNS tumour or metastases) and/or receiving anticoagulation therapy may be at an increased risk of developing intracerebral bleeding (including fatal outcomes) while receiving Torisel, the company informed.

The most common (incidence >30 per cent) adverse reactions observed with Torisel are: rash (47 per cent), asthenia (51 per cent), mucositis (41 per cent), nausea (37 per cent), oedema (35 per cent), and anorexia (32 per cent). The most common laboratory abnormalities (incidence >30 per cent) are anaemia (94 per cent), hyperglycemia (89 per cent), hyperlipemia (87 per cent), hypertriglyceridemia (83 per cent), elevated alkaline phosphatase (68 per cent), elevated serum creatinine (57 per cent), lymphopenia (53 per cent), hypophosphatemia (49 per cent), thrombocytopenia (40 per cent), elevated AST (38 per cent), and leukopenia (32 per cent).

Most common Grades 3/4 adverse events included asthenia (11 per cent), dyspnoea (9 per cent), haemoglobin decreased (20 per cent), lymphocytes decreased (16 per cent), glucose increased (16 per cent), phosphorus decreased (18 per cent) and triglycerides increased (44 per cent).

Strong inducers of CYP3A4/5 (e.g., dexamethasone, rifampin) and strong inhibitors of CYP3A4 (eg, ketoconazole, atazanavir) may decrease and increase concentrations of the major metabolite of Torisel, respectively. If alternatives cannot be used, dose modifications of Torisel are recommended.

Wyeth Pharmaceuticals, a division of Wyeth, has leading products in the areas of women's health care, infectious disease, gastrointestinal health, central nervous system, inflammation, transplantation, haemophilia, oncology, vaccines and nutritional products.