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This combination therapy, investigated by the European Organisation for Research and Treatment of Cancer (EORTC), consists of the antimetabolite fluorouracil (5-FU), the recombinant cytokine aldesleukin (interleukin-2), and interferon alfa-2a. It was primarily evaluated as an adjuvant treatment for patients with high-risk renal cell carcinoma (RCC) following surgical nephrectomy. Fluorouracil acts as a small molecule thymidylate synthase inhibitor, disrupting DNA synthesis and repair in tumor cells. Aldesleukin and interferon alfa-2a serve as immunomodulatory agents that stimulate T-cell and natural killer (NK) cell activity to enhance the immune system's ability to clear residual microscopic disease. The Phase 3 EORTC 30992 trial compared this triple combination to observation alone; however, the study concluded that the regimen did not significantly improve disease-free or overall survival in the adjuvant setting.
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