Clinical and immune modulatory effects of alternative weekly interleukin-2 and interferon alfa-2a in patients with advanced renal cell carcinoma and melanoma
Autor: | W Fierz, L. M. Jost, Gabriella Pichert, Rolf A. Stahel |
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Rok vydání: | 1991 |
Předmět: |
Adult
Male Interleukin 2 Cancer Research medicine.medical_specialty medicine.medical_treatment Phases of clinical research Alpha interferon Interferon alpha-2 Gastroenterology Drug Administration Schedule Autoimmune thyroiditis Renal cell carcinoma Internal medicine medicine Carcinoma Humans Killer Cells Lymphokine-Activated Carcinoma Renal Cell Melanoma Interferon alfa business.industry Interferon-alpha HLA-DR Antigens Immunotherapy Middle Aged medicine.disease Kidney Neoplasms Recombinant Proteins Killer Cells Natural Oncology Immunology Interleukin-2 Female business Research Article medicine.drug |
Zdroj: | British Journal of Cancer |
ISSN: | 1532-1827 0007-0920 |
Popis: | The clinical and immune modulatory effects of interleukin-2 (IL-2) and interferon (INF) alfa-2a were examined in a phase II study in patients with metastatic renal cell carcinoma (six patients) and melanoma (eight patients). Treatment consisted in IL-2 3 MU/m2 continuous infusion days 1-4 and INF alfa-2a 6 MU/m2 subcutaneously day 1 and 4, both given on alternate weeks. Tumour response was assessed after four cycles of treatment or earlier, if necessary. Patients with stable disease or response were to be continued for another nine cycles or up to disease progression. The 14 patients received a total of 60 cycles of treatment. Major toxicities (WHO Grade III/IV) were fever, capillary leak syndrome with hypotension, nausea and vomiting, erythema with pruritus, leuco- and thrombopenia and sepsis with staphylococcus aureus. Five of 14 patients (36%) developed a self limiting autoimmune thyroiditis with HLA-DR expression on thyrocytes. Long term treatment toxicity was moderate with an average weight loss of 5% and an average fall in Karnofsky index of 10% compared to baseline. No responses were seen in renal cell carcinoma, two patients with melanoma had a partial and two a minor response with a duration of 1-7 months. Serial measurements of immune modulatory parameters showed a functional response to treatment with an increase of NK- and LAK-activity during the first two cycles, followed by a plateau and decrease during the third and fourth cycles. These findings were paralleled by a successive decline in treatment induced INF gamma response. These findings suggest, that alternative weekly treatment with IL-2 and INF alfa-2a results in an exhaustion of lytic capacity of NK- and LAK-cells and an attenuation of secondary cytokine release. Images Figure 2 |
Databáze: | OpenAIRE |
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