In vivo effects of combination treatment with recombinant interferon-gamma and -alpha in metastatic melanoma.
The toxicity and therapeutic efficacy of the combination of recombinant interferon gamma (rIFN-gamma) and alpha (rIFN-alpha) was investigated in 15 patients with metastatic melanoma. Patients were treated with an escalating dose of rIFN-gamma and a fixed dose of rIFN-alpha administered s.c. 3 times a week. The maximum dose was well tolerated. The median survival time of the patients was 7 months; no clinical remissions were observed. In the majority of cases, expression of HLA class-I and -II antigens on the patients' peripheral blood lymphocytes and monocytes increased markedly during treatment. An increase in HLA-DR expression of peripheral blood T lymphocytes was correlated with a longer survival time. This suggests that activation of T lymphocytes may have a favourable influence on the course of metastatic disease. The in vitro anti-proliferative activity of IFNs on melanoma cell lines isolated from melanoma metastases during treatment of 3 patients was determined. In contrast to the lack of in vivo anti-tumour effect in patients, both rIFN-gamma and rIFN-alpha inhibited DNA synthesis of these melanoma cell lines in vitro, combined IFNs acting synergistically. Anti-proliferative activity observed in vitro occurred at IFN concentrations below the peak serum levels achieved in vivo.
Osanto
S
S
Department of Clinical Oncology, University Hospital, Leiden, The Netherlands.
Jansen
R
R
Naipal
A M
AM
Gratama
J W
JW
van Leeuwen
A
A
Cleton
F J
FJ
D002455:Cell Division / Q000187:drug effects; D002469:Cell Separation; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D007279:Injections, Subcutaneous; D007370:Interferon Type I / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D007371:Interferon-gamma / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008545:Melanoma / Q000276:immunology / Q000378:metabolism / Q000401:mortality / Q000628:therapy*; D009362:Neoplasm Metastasis; D011994:Recombinant Proteins; D013997:Time Factors; D014407:Tumor Cells, Cultured
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007370:Interferon Type I; D011994:Recombinant Proteins; D007371:Interferon-gamma