INTERLEUKIN-2 AND INTERFERON ALPHA-2A DO NOT IMPROVE ANTITUMOR-ACTIVITY OF 5-FLUOROURACIL IN ADVANCED COLORECTAL-CANCER

Treatment using a combination of 5-fluorouracil (5-FU), interferon-alp ha (IFN alpha-2a) and interleukin 2 (IL-2) has been shown to mediate d isease regression in selected patients with advanced colorectal cancer . This phase II study was designed to evaluate the anti-tumour activit y and toxicity of the combination of IL-2, IFN alpha-2a and 5-FU in pa tients with advanced colorectal cancer. Forty-four patients with metas tatic colorectal cancer were treated, predominantly on an outpatient b asis, with subcutaneous IFN alpha-2a and IL-2 three times per week fol lowed by once a week bolus intravenous 5-FU injections. There were six (14%) partial responses among the 43 evaluable patients [95% confiden ce interval (CI) 5-28%]. Twenty-four patients had stable disease (56%) and 13 patients (30%) showed progressive disease. The median time to progressive disease in 43 patients was 19 weeks (range 2-72 weeks) and in responders 34 weeks (range 24-30 weeks). The median overall surviv al was 47 weeks (range 2-85 weeks) and in responders 60 weeks (range 3 5-71 weeks). Treatment-related toxic effects included fatigue, nausea and vomiting. Granulocytopenia was the main reason for the dose reduct ions or treatment interruptions in 32 out of 44 patients. One patient died of toxicity due to renal failure. Serial assessments of immunophe notyping and cytolytic activities of peripheral blood lymphocytes did not show changes in the numbers of circulating natural killer (NK) cel ls or in the levels of NK and lymphokine-activated killer (LAK) cytoly tic activities. This regimen of IL-2 and IFN alpha-2a with 5-FU has on ly modest anti-tumour activity in advanced colorectal cancer.