An article published Online First and in an upcoming edition of The Lancet reports that combination therapy for renal cell carcinoma does not improve overall or progression-free survival compared with single therapy using interferon alfa-2a alone. Still, the combined regimen might still have a function because it can produce remissions that are of clinically relevant length in some patients. As a result, identification of these patients is essential. The article is the work of Professor Martin E Gore, Department of Medicine, Royal Marsden Hospital NHS Trust, London, and colleagues.

Two percent of all malignant tumours in adults are renal cell carcinomas. Thirty percent of patients with renal cell carcinoma present with metastatic disease (secondary tumours). Also, half of patients who apparently have localised disease at diagnosis develop metastases later. Average survival for patients with advanced disease is ten months and five-year survival is fifteen percent. The immunotherapy regimen that has given the highest response rates in metastatic renal cell carcinoma is a combination of interferon alfa-2a, interleukin-2, and fluorouracil. The authors compared in this study interferon alfa-2a alone with combined interferon alfa-2a, interleukin-2, and fluorouracil.

A total of fifty centres across eight countries took part in this randomised trial. Overall, 1,006 treatment-naive patients diagnosed with advanced metastatic renal cell carcinoma were assigned to receive treatment. They received interferon alfa-2a alone or combination therapy with interferon alfa-2a, interleukin-2, and fluorouracil. The primary endpoint was overall survival.

At random, 502 patients were assigned to receive interferon alfa-2a and 504 to receive combined treatment. Average monitoring was just over three years. Median overall survival was 18•8 months for patients receiving interferon alfa-2a. It was 18•6 months for those receiving combination therapy. Overall survival was similar between the two groups. Serious adverse events were reported in 113 (23 percent) patients receiving interferon alfa-2a and 131 (26 percent) of those receiving combined treatment.

Professor Gore comments: "Although combination therapy does not improve overall or progression-free survival compared with interferon alfa-2a alone, immunotherapy might still have a role because it can produce long remissions in a small number of patients. Identification of these patients is of considerable importance."

He explains: "The individualisation of cancer therapies based on identifying predictive markers within tumours is important. This particularly applies to immunotherapy for kidney cancer where there can be considerable benefit but only for a small percentage of patients."

"Interferon alfa-2a versus combination therapy with interferon alfa-2a, interleukin-2, and fluorouracil in patients with untreated metastatic renal cell carcinoma (MRC RE04/EORTC GU 30012): an open-label randomised trial"
Martin E Gore, Clare L Griffin, Barry Hancock, Poulam M Patel, Lynda Pyle, Michael Aitchison, Nicholas James, Roderick T D Oliver, Jozef Mardiak, Tahera Hussain, Richard Sylvester, Mahesh K B Parmar, Patrick Royston, Peter F A Mulders
DOI: 10.1016/S0140-6736(09)61921-8
The Lancet

Written by Stephanie Brunner (B.A.)