title: A phase I trial of recombinant interleukin-2 combined with recombinant interferon-gamma in patients with cancer.
abstract: Twenty-six patients with metastatic cancer were entered into a phase I trial of concurrent recombinant interleukin-2 (IL-2) and recombinant interferon-gamma (IFN-gamma). IL-2 was administered as a continuous intravenous infusion for 5 days. IFN-gamma was administered by a daily intramuscular (IM) injection during the 5 days of IL-2 administration. Treatment was repeated twice after 9-day rest periods. After a 2-week rest, patients without evidence of tumor progression were retreated. Natural killer (NK)- and lymphokine-activated killer (LAK)-cell activity were assayed in each patient before treatment, on day 1, and on day 5 of each cycle. Constitutional symptoms occurred in most patients but were not dose-limiting. Other toxicities included hypotension responsive to fluids, transient elevations in liver function tests, erythema/pruritus, eosinophilia, and transient leukopenia/thrombocytopenia. The maximum-tolerated dose (MTD) of the combination was 1 x 10(6) U/m2/d of IL-2 combined with 0.50 mg/m2/d of IFN-gamma. The dose-limiting toxicity was pulmonary manifesting as rales and shortness of breath. The dose of the combination that resulted in the optimal generation of in vivo LAK-cell activity was a dose of at least 0.25 mg/m2/d of IFN-gamma combined with 1 x 10(6) U/m2/d of IL-2. Objective clinical responses were seen in five of 26 patients. These included a partial response of 2 months duration in a patient with non-Hodgkin's lymphoma (NHL), mixed responses in a patient with NHL and two patients with renal cell carcinoma (RCC), and an ongoing assessable response in a patient with bone metastases from RCC. The recommended dose for phase II trials of this combination is 0.50 mg/m2 of IFN-gamma and 1 x 10(6) U of IL-2.
authors.affiliation: Department of Internal Medicine, Wayne State University School of Medicine, Harper Hospital, Detroit, MI 48201.
authors.forename: B G
authors.initials: BG
authors.lastname: Redman
authors.forename: L
authors.initials: L
authors.lastname: Flaherty
authors.forename: T H
authors.initials: TH
authors.lastname: Chou
authors.forename: A
authors.initials: A
authors.lastname: al-Katib
authors.forename: M
authors.initials: M
authors.lastname: Kraut
authors.forename: S
authors.initials: S
authors.lastname: Martino
authors.forename: B
authors.initials: B
authors.lastname: Chen
authors.forename: J
authors.initials: J
authors.lastname: Kaplan
authors.forename: M
authors.initials: M
authors.lastname: Valdivieso
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage; D007376:Interleukin-2 / Q000008:administration & dosage; D007680:Kidney Neoplasms / Q000188:drug therapy; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects; D007694:Killer Cells, Natural / Q000187:drug effects; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage
chemical_list: D007376:Interleukin-2; D011994:Recombinant Proteins; D007371:Interferon-gamma