A phase II trial of interferon alpha-2A plus fluorouracil in advanced renal cell carcinoma

Summary In vitro studies have documented the synergistic activity of interferon (IFN) and fluorouracil (5-FU) in human cancer cell lines, and recent clinical trials have demonstrated the efficacy of this combination in metastatic colon cancer. The current study was undertaken to evaluate the combination of IFN alpha-2a plus 5-FU in previously untreated patients with metastatic renal cell carcinoma. From May 1990 through August 1990, 14 patients with metastatic renal cell carcinoma were treated with 5-FU 750 mg/m² day continuous infusion IV days 1–5, followed by weekly IV infusions of 5-FU 750 mg/m² beginning on day 12. Patients concurrently received IFN alpha-2a 9×10⁶ IU subcutaneously 3 times per week beginning on day 1. The median age of patients treated was 57 (range 38–80) with a median Karnofsky performance status of 90 (range 60–100). Sites of metastases included lung only in 6 patients, liver only in 1 patient, 1 patient had bilateral disease at presentation, and the remaining patients had multiple sites of metastases. The median duration of therapy was 2 months. The predominant toxicities seen were stomatitis, nausea, flu-like symptoms and neurotoxicity. The only grade IV toxicity observed was severe vomiting in 1 patient, though 5 patients discontinued therapy within 2 months because of poor subjective response. With a minimum follow-up of 13 months no objective responses were seen. Thirteen of the 14 patients have had progressive disease and 11 have died. The median time to progression was 2 months (range 0.5–6 months) and the median survival was 5 months (range 2–14.5+months). We conclude that at this dose and schedule, IFN alpha-2a plus 5-FU is ineffective in the treatment of advanced renal cell carcinoma.From the Hoosier Oncology Group, the Walter Cancer Institute, Indianapolis, Indiana and the Department of Medicine, Indiana University, Indianapolis, USA.