Interferon Alfa With or Without Interleukin-2 and Fluorouracil in Treating Patients With Advanced Metastatic Kidney Cancer

Interferon Alfa With or Without Interleukin-2 and Fluorouracil in Treating Patients With Advanced Metastatic Kidney Cancer

A Randomized Controlled Trial of Interferon-alpha, Interleukin-2 and 5-Fluorouracil vs. Interferon-alpha Alone in Patients With Advanced Renal Cell Carcinoma

RATIONALE: Interferon alfa may interfere with the growth of tumor cells. Interleukin-2 may stimulate a person's white blood cells to kill tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining interferon alfa with interleukin-2 and fluorouracil may kill more tumor cells. It is not yet known whether interferon alfa is more effective with or without interleukin-2 and fluorouracil in treating metastatic kidney cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of interferon alfa combined with interleukin-2 and fluorouracil to that of interferon alfa alone in treating patients who have advanced metastatic kidney cancer.

OBJECTIVES: Compare progression-free and overall survival of patients with advanced metastatic renal carcinoma treated with interferon alfa with or without interleukin-2 and fluorouracil. Compare the toxicity of these regimens in these patients. Assess the quality of life of patients treated with these regimens. OUTLINE: This is a randomized, open-label, multicenter study. Patients are randomized to 1 of 2 treatment arms. Arm I (Interferon alfa monotherapy): Patients receive interferon alfa subcutaneously (SC) on days 1, 3, and 5. Treatment continues weekly for at least 9 weeks in the absence of disease progression or unacceptable toxicity. Arm II (Interferon alfa, interleukin-2, and fluorouracil combination therapy): Patients receive interferon alfa SC on day 1 of weeks 1 and 4 and days 1, 3, and 5 of weeks 2, 3, 5, 6, 7, and 8. Patients also receive interleukin-2 SC twice daily on days 3-5 of weeks 1 and 4 and once daily on days 1, 3, and 5 of weeks 2 and 3. Patients then receive fluorouracil IV on day 1 of weeks 5-8. Treatment repeats every 10 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, at 9, 19, and 26 weeks, and then at 8 months. Patients are followed at 8, 10, and 12 months, every 4 months for 1 year, and then every 6 months thereafter. PROJECTED ACCRUAL: A total of 670 patients (335 per treatment arm) will be accrued for this study.

DISEASE CHARACTERISTICS: Histologically confirmed renal cell carcinoma Advanced metastatic disease that requires treatment Measurable disease (single bone lesions not included) No brain metastasis PATIENT CHARACTERISTICS: Age 18 to 81 Performance status WHO 0-1 Life expectancy More than 12 weeks Hematopoietic WBC greater than 3,000/mm^3 Platelet count greater than 100,000/mm^3 Hemoglobin greater than 10 g/dL Hepatic Not specified Renal Not specified Cardiovascular No myocardial infarction within the past 6 months No unstable angina pectoris Other Not pregnant or nursing Fertile patients must use effective contraception during and for at least 6 months after study participation No other concurrent disease or prior malignancy that would preclude study treatments or comparisons No concurrent active infection requiring antibiotics PRIOR CONCURRENT THERAPY: Biologic therapy No prior biologic therapy Chemotherapy No prior chemotherapy Endocrine therapy No prior endocrine therapy No concurrent corticosteroids Radiotherapy At least 4 weeks since prior radiotherapy Surgery Prior resection of the primary tumor recommended but not required No prior major organ allografts

Gore ME, Griffin CL, Hancock B, Patel PM, Pyle L, Aitchison M, James N, Oliver RT, Mardiak J, Hussain T, Sylvester R, Parmar MK, Royston P, Mulders PF. 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. Lancet. 2010 Feb 20;375(9715):641-8. doi: 10.1016/S0140-6736(09)61921-8. Epub 2010 Feb 10.

Gore ME: Interferon-α (IFN), interleukin-2 (IL2) and 5-fluorouracil (5FU) vs IFN alone in patients with metastatic renal cell carcinoma (mRCC): results of the randomised MRC/EORTC RE04 trial. [Abstract] J Clin Oncol 26 (Suppl 15): A-5039, 2008.