Immunochemotherapy using Interleukin-2, Interferon-alpha, and 5-fluorouracil for Advanced Renal Cell Carcinoma

Lim, Daejung; Lee, Seung Bae; Kim, Dae Young; Park, Moon Soo; Lee, Sang Eun

Abstract

PURPOSE: The role of immunotherapy in the treatment of patients with advanced renal cell carcinoma(RCC) is being evaluated by a number of investigators. In this study, we evaluated the efficacy and toxicity of a low-dose subcutaneous regimen of interferon-alpha(IFN-alpha) in combination with intravenous administration of 5-fluorouracil(5-FU) with or without interleukin-2 (IL-2) in patients with advanced RCC.
MATERIALS AND METHODS
16 patients with advanced RCC were treated with an 8-week cycle of 6 to 9 MU/M2 IFN-alpha given 1 to 3 times a week during the 8 week period, and sequentially combined with 5 to 20 MU/M2 IL-2 given 3 times a week for 4 weeks and 750mg/M2 5-FU once a week for 4 weeks. 5 patients were treated with only IFN-alpha and 5-FU. Treatment schedule was identical except for the exclusion of IL-2 in this group. Among those 16 patients treated with 3-drug regimen(including IL-2), 10 patients had measurable metastatic lesions, and 4 patients had measurable metastatic lesions among 5 patients treated with 2-drug regimen(without IL-2).
RESULTS
Among 19 consecutive men and 2 women treated, 14 had measurable metastatic lesion. 10 out of 14 patients with measurable metastatic lesions were treated with 3- drug regimen, and objective tumor regressions were achieved in 4 patients(40%) consisting of complete response in 1(10%) and partial response in the other 3(30%). Metastatic sites were lung in 3 patients, bone in 1 patient. 3 of the 4(75%) patients with pulmonary metastasis showed complete or partial response. Median response duration(complete plus partial response) was 14.3 months(range 11 to 22+). Stable disease lasting 3 months was noted in 1 patients(10%). Other 4 patients out of 14 patients with measurable metastatic lesions were treated with 2-drug regimen, and partial remission lasting 9 months was noted in 1 patient(25%). There were only mild to moderate side effects; maximum toxicity grade of 0 in 10 patients, grade I in 3, II in 7, III in 1 according to the World Health Organization classification. None of the patients experienced major IL-2 related toxicity and no toxic deaths occurred.
CONCLUSIONS
This combination immunochemotherapy may be a promising regimen with modest toxicity in advanced RCC. The most favorable response can be expected in pulmonary metastasis. Most of side effects were tolerable. Three-drug regimen including IL-2 showed better response rate than two-drug regimen, suggesting a major role of IL-2. A large prospective randomized trials are required to confirm whether the combination immunochemotherapy has an effect on advanced RCC or not.