Immunotherapy with concurrent subcutaneous GM-CSF, low-dose IL-2 and IFN-α in patients with progressive metastatic renal cell carcinoma

N. Verra, R. Jansen, G. Groenewegen, H. Mallo, M. J. Kersten, A. Bex, F. A. Vyth-Dreese, J. Sein, W. Van De Kasteele, W. J. Nooijens, M. De Waal, S. Horenblas, G. C. De Gast*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

30 Citations (Scopus)

Abstract

The purpose of the study was to determine toxicity, efficacy and immunologic effects of concurrent subcutaneous injections of low-dose interleukin-2 (LD-IL-2), granulocyte-monocyte colony-stimulating factor (GM-CSF) and interferon-α 2b (IFNα) in progressive metastatic renal cell carcinoma. In a multicentre phase II study, 59 evaluable patients received two to six cycles of subcutaneous IL-2 (4 mlU m-2), GM-CSF (2.5 μg kg-1) and IFNα (5 mlU flat-1) for 12 days per 3 weeks with evaluation after every two cycles. Cycles were repeated in responding or stable patients. Data were analysed after a median of 30 months follow-up (range 16-48 months). In 42 patients, the immunologic response was studied and related to response and survival. The main toxicity were flu-like symptoms, malaise and transient liver enzyme elevations, necessitating IL-2 reduction to 2 mlU m-2 in 29 patients, which should be considered the maximal tolerable dose. The response was 24% (eight out of 34, three complete response (CR), five partial response (PR)) in patients with metachronic metastases and 12% (three out of 25, 2CR, IPR) in patients with synchronic metastases. Overall response was 19% (11 out of 59). Median survival was 9.5 months. All tested patients showed expansion and/or activation of lymphocytes, T cells and subsets, NK cells, eosinophils and monocytes. Pretreatment HLA-DR levels on monocytes and number of CD4+ HLA-DR+ cells correlated with response. Pretreatment number of CD4+ HLA-DR+ cells and postimmunotherapy levels of lymphocytes, CD3+, CD4+ and CD8+ T cells, but not of NK or B cells, correlated with prolonged survival. Immunotherapy with concurrent subcutaneous GM-CSF, LD-IL-2 and IFNα has limited toxicity, can be given as outpatient treatment and can induce durable CR. Response and survival with this form of immunotherapy seem to be more dependent on expansion/activation oft cells than of NK cells.

Original languageEnglish
Pages (from-to)1346-1351
Number of pages6
JournalBritish Journal of Cancer
Volume88
Issue number9
DOIs
Publication statusPublished - 6 May 2003

Keywords

  • Immunotherapy
  • Multicentre phase II study
  • Renal cell carcinoma

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