Immunochemotherapy with interleukin-2, interferon-alpha and 5-fluorouracilfor progressive metastatic renal cell carcinoma: a multicenter phase II study

In patients with metastatic renal cell carcinoma response rates of 7-26% ha ve been achieved with immunotherapy. A high response rate of 48% in 35 pati ents has been reported for treatment with the combination of interferon-alp ha (IFN-alpha), interleukin-2 (IL-2) and 5-fluorouracil (5-FU) (Atzpodien e t al (1993a) fur J Cancer 29A: S6-8). We conducted a multicentre phase II s tudy to confirm these results. Metastatic renal cell carcinoma patients wer e treated as outpatients with an 8-week treatment cycle. Recombinant human IL-2 20 MU m(-2) was administered subcutaneously (s.c.) three times a week (t.i.w) in weeks 1 and 4 and 5 MU m(-2) t.i.w. in weeks 2 and 3. Recombinan t human IFN-alpha 2a 6 MU m(-2) was administered s.c. once in weeks 1 and 4 and t.i.w. in weeks 2 and 3, and 9 MU m(-2) t.i.w. in weeks 5-8. 5-FU (750 mg m(-2)) was given as a bolus injection intravenous once a week in weeks 5-8. The treatment cycle was repeated once in case of response or minor res ponse. Fifty-two patients entered the study. All had undergone a nephrectom y and had progressive metastatic disease. The median WHO-performance status was 1, the median number of metastatic sites was 2 (range 1-5) and the med ian time between the diagnosis of the primary tumour and the start of treat ment was 12.9 months (range 1-153), Among the 51 patients, including four p atients with early progressive disease, who were evaluable for response, th e response rate was 11.8% (95% confidence interval (CI) 2.9-20.7%), with no complete responses. Median duration of response was 8.3 (range 3.8-22.4+) months. Median survival was 16.5 (range 1.8-30.5+) months. Grade 3/4 toxici ty (WHO) occurred in 29/52 (55.8%) of the patients in cycle 1 and in 6/16 ( 37.5%) of the patients in cycle 2, If consisted mainly of anorexia, fatigue , nausea, fever and leucocytopenia. We cannot confirm the high response rat e in patients with metastatic renal cell carcinoma treated with the combina tion of IFN-alpha, IL-2 and 5;FU, as described by Atzpodien et al. (C) 2000 Cancer Research Campaign.