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

Overview

Journal Lancet

Publisher Elsevier

Specialty General Medicine

Date 2010 Feb 16

PMID 20153039

Citations 38

Authors

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

Affiliations

Soon will be listed here.

Abstract

Background: In metastatic renal cell carcinoma combinations of interferon alfa-2a, interleukin-2, and fluorouracil produce higher response rates and longer progression-free survival than do single agents. We aimed to compare overall survival in patients receiving combination treatment or interferon alfa-2a.

Methods: RE04/30012 was an open-label randomised trial undertaken in 50 centres across eight countries. 1006 treatment-naive patients diagnosed with advanced metastatic renal cell carcinoma were randomly allocated (1 to 1) by minimisation to receive interferon alfa-2a alone or combination therapy with interferon alfa-2a, interleukin-2, and fluorouracil. Treatment was not masked. The primary endpoint was overall survival. Treatment groups were compared with a non-stratified log-rank test. Analysis was by intention to treat. This study is registered, number ISRCTN 46518965.

Findings: 502 patients were randomly assigned to receive interferon alfa-2a and 504 to receive combined treatment. Median follow-up was 37.2 months (24.8-52.3). Median overall survival was 18.8 months (17.0-23.2) for patients receiving interferon alfa-2a versus 18.6 months (16.5-20.6) for those receiving combination therapy. Overall survival did not differ between the two groups (hazard ratio 1.05 [95% CI 0.90-1.21], p=0.55; absolute difference 0.3% (-5.1 to 5.6) at 1 year and 2.7% (-8.2 to 2.9) at 3 years). Serious adverse events were reported in 113 (23%) patients receiving interferon alfa-2a and 131 (26%) of those receiving combined treatment.

Interpretation: 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 remissions that are of clinically relevant length in some patients. Identification of patients who will benefit from immunotherapy is crucial.

Funding: UK Medical Research Council.

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