Combination therapy with interferon-gamma and interleukin-2 for the treatment of metastatic melanoma.
The toxicity and clinical response to treatment with the combination of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) in patients with metastatic melanoma was evaluated. From May 1993 through February 1994, 20 patients were treated with 24 courses of IFN-gamma with or without IL-2. A 7-day course of subcutaneous IFN-gamma alone was administered to cohorts of two or three patients each at doses of 0.1, 0.2, or 0.3 mg/m2. Thirteen patients received escalating doses of IFN-gamma between 0.2 and 0.5 mg/m2 followed by the intravenous (i.v.) administration of IL-2 (720,000 IU/kg) given three times a day. A treatment course consisted of two cycles (maximum of 15 doses of IL-2 per cycle) separated by a 10-day interval. Five additional patients were treated with five courses of IFN-gamma, IL-2, and tumor-infiltrating lymphocytes (TILs). All patients treated had the diagnosis of metastatic melanoma. The maximal tolerated dose of subcutaneous IFN-gamma was established at 0.3 mg/m2 with dose-limiting hepatotoxicity. Immunohistochemistry analyses showed detectable upregulation of MHC class I alleles in one (8%) of 12 patients. Two of 20 patients who received the combination of IFN-gamma and IL-2 had responses, one partial and one complete response. The duration of response was 7 months for the partial response and 12 months for the complete response. IFN-gamma was tolerated with minimal side effects of nausea, vomiting, malaise, and decreased hematopoiesis. No increased toxicities were found with the combination treatment, as compared with IL-2 alone. One death occurred on the third day of treatment with IFN-gamma alone from hemorrhage into brain metastases. There were no responders in the five patients who received the combination treatment of TIL, IL-2, and IFN-gamma. From these findings, we conclude that further studies looking at this combination treatment are not warranted.
Kim
C J
CJ
Surgery Branch, Clinical Oncology Program, National Cancer Institute, Bethesda, Maryland, USA.
Taubenberger
J K
JK
Simonis
T B
TB
White
D E
DE
Rosenberg
S A
SA
Marincola
F M
FM
D000328:Adult; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008545:Melanoma / Q000737:chemistry / Q000378:metabolism / Q000556:secondary* / Q000628:therapy*; D008875:Middle Aged; D012878:Skin Neoplasms / Q000737:chemistry / Q000378:metabolism / Q000556:secondary* / Q000628:therapy*
D007376:Interleukin-2; D007371:Interferon-gamma