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- Title
A phase I study of recombinant human interleukin-2 and alpha-interferon-2a in patients with renal cell cancer, colorectal cancer, and malignant melanoma.
- Authors
Mittelman, A.; Huberman, M.; Puccio, C.; Fallon, B.; Tessitore, J.; Savona, S.; Eyre, R.; Gafney, E.; Wick, M.; Skelos, A.; Arnold, P.; Ahmed, T.; Groopman, J.; Arlin, Z.; Zeffren, J.; Levitt, D.
- Abstract
Preclinical data suggest synergy of interleukin-2 (IL-2) combined with alpha-interferon (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 10(5) units (U)/m2/d for 4 days plus IFN at 6 X 10(6) 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 X 10(6) U/m2/d with three to eight patients at each dose level, at each of the two participating institutions. The dose of IFN was 6 X 10(6) U/m2 days 1 and 4 for all but five patients whose IFN dose was doubled to 12 X 10(6) 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 III 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 X 10(6) U/m2/d of IL-2 and 6 X 10(6) U/m2 of alpha-IFN.
- Subjects
ANTINEOPLASTIC agents; CLINICAL trials; COLON tumors; DRUG synergism; DRUG administration; CLINICAL drug trials; FATIGUE (Physiology); HYPOTENSION; INTERLEUKIN-2; KIDNEY tumors; LYMPHOMAS; MELANOMA; PROTEINS; RECOMBINANT proteins; RECTUM tumors; RENAL cell carcinoma; SKIN tumors; TUMORS
- Publication
Cancer (0008543X), 1990, Vol 66, Issue 4, p664
- ISSN
0008-543X
- Publication type
journal article
- DOI
10.1002/1097-0142(19900815)66:4<664::AID-CNCR2820660411>3.0.CO;2-D