Preclinical data suggest synergy of interleukin-2 (IL-2) combined with alphainterferon (IFN). In addition, toxicities of IL-2 may be decreased by intermittent continuous infusion. The purpose of this trial was to determine the maximum tolerated dose (MTD) of recombinant IL-2 combined with alpha-IFN in patients with renal cancer, colon cancer, melanoma, and malignant B-cell disease. IL-2 was given by continuous i.v. infusion at an initial dose of 5 x lo5 units (U)/m2/d for 4 days plus IFN at 6 > lofi U/m2/d intramuscularly days 1 and 4 weekly for 4 weeks.
Patients who achieved a response or stable disease received an additional 4 weeks of therapy. IL-2 doses were increased to 1, 2, 3, 5, and 7 lo6 U/mz/d with three to eight patients at each dose level, at each of the two participating institutions. The dose of IFN was 6 x lo6 U/m2 days 1 and 4 for all but five patients whose IFN dose was doubled to 1 2 A lofi U/m2/d. Forty-three patients were entered on this study with 34 completing at least 4 weeks of therapy. Six patients were taken off study because of Grades I11 or IV pulmonary, neurologic, or cardiac toxicity; one for progressive disease; one for CNS metastases, and one for personal reasons. All of the toxicities were reversible. Chills and fever were universal, especially on days 1 and 4. Mild and moderate nausea, vomiting, diarrhea, anorexia, malaise, and cutaneous erythema were present in most patients. Fluid retention and occasional pleural effusions were observed at the higher IL-2 doses but were not dose-limiting. Significant hypotension associated with oliguria was seen, and these patients were treated with vasopressors and colloids. None of the patients required ICU admission. Thirty-four patients were evaluable for response. There were 4/18 (22%) renal cell patients who experienced a partial response. No responses were seen in patients with melanoma, lymphoma, or colorectal cancer. The combined debilitating symptoms of fatigue, diarrhea, hypotension, fluid retention, and anorexia defined the MTD as 5 >. lofi U/m2/d of IL-2 and 6 X lo6 U/mz of alpha-IFN. Cancer 66:664-669,1990. ATURAL INTERLEUKIN-? (IL-7) IS a lymphokine that N is produced by T lymphocytes and induces proliferative and functional changes in T cells, B cells, and natural killer cells.'.' DNA engineering has permitted