Interleukin-2 followed by fluorouracil and folinic acid in refractory colorectal cancer--results of a clinical phase II study.

: In a clinical phase II study, 23 patients with progressive metastatic colorectal cancer and failure after first-line chemotherapy with fluorouracil (5-FU) and folinic acid (FA) were treated with a 5-day continuous infusion of recombinant interleukin-2 (IL-2), 3 x 10(6) cetus U/m2/d, followed after a rest period of 2 days by 5-FU, 600 mg/m2/d, and FA, 300 mg/m2/d over an additional 3 days. After two to four treatment cycles, eight of 22 evaluable patients (36%) revealed antitumor responses, with three partial remissions and five minor responses or stable disease. Side effects consisted most frequently of fever, nausea and vomiting, an elevation of liver enzymes, hypotension, and skin toxicity, and required a 50% reduction of IL-2 dose in 17 of 71 treatment courses (24%). In four of the 23 patients (18%), treatment had to be stopped completely. These data indicate a significant antitumor activity of IL-2 combined with 5-FU/FA therapy in chemotherapy-resistant colorectal cancer. Hence, in spite of a substantial treatment-related toxicity, further studies are warranted to substantiate these findings and to elucidate the underlying mechanisms of the IL-2-5-FU/FA combination therapy.