INTERLEUKIN-2 IN COMBINATION WITH INTERFERON-ALPHA AND 5-FLUOROURACILFOR METASTATIC RENAL-CELL CANCER

Recent clinical trials for the biological therapy of solid tumours hav e used recombinant human cytokines in combination with conventional ch emotherapy. In patients with progressive metastatic renal cell carcino ma, we established a three-drug combination comprising interferon-alph a (IFN-alpha), interleukin-2 (IL-2) and 5-fluorouracil (5-FU), using a regimen which allows outpatient therapy. Treatment consisted of 8 wee ks each of IFN-alpha [6-9 MU/m2 once to three times weekly subcutaneou sly (sc)] combined sequentially with IL-2 (5-20 MU/m2 thrice weekly sc for 4 weeks) and 5-FU [750 mg/m2 intravenously (iv) weekly for 4 week s]. Among the first 35 patients treated, there were 4 complete (11.4%) and 13 partial responders (37.1%), with an overall objective response rate of 48.6% (95% confidence interval 32-66%). Regressions occurred in local relapse, in lung, lymph node, bone, pleural, renal and thyroi d metastases. Median response duration was calculated at 7+ months. An additional 13 patients (37.1%) were stable throughout therapy and the reafter (median of 6+ months). Response rate of this three-drug combin ation regimen compared favourably with single agent IFN-alpha (objecti ve response rate approximately 16%) and against the sc IFN-alpha/IL-2 combination (objective response rate approximately 28%). Systemic toxi city was mild to moderate with no severe 5-FU-related mucositis and no dose-limiting adverse effects of se IL-2. While the exact mechanisms of the potentially additive or synergistic effects of 5-FU and IFN-alp ha/IL-2 remain to be established in more detail, it appears that the s equential use of IFN-alpha/IL-2 and IFN-alpha/5-FU in metastatic renal carcinoma further enhances the therapeutic index of IFN-alpha/IL-2-ba sed biological therapy. Based on the present data. combined biochemoth erapy may be a promising new approach to the therapy of advanced renal cancer.