TY - JOUR
T1 - Immunotherapy with concurrent subcutaneous GM-CSF, low-dose IL-2 and IFN-α in patients with progressive metastatic renal cell carcinoma
AU - Verra, N.
AU - Jansen, R.
AU - Groenewegen, G.
AU - Mallo, H.
AU - Kersten, M. J.
AU - Bex, A.
AU - Vyth-Dreese, F. A.
AU - Sein, J.
AU - Van De Kasteele, W.
AU - Nooijens, W. J.
AU - De Waal, M.
AU - Horenblas, S.
AU - De Gast, G. C.
PY - 2003/5/6
Y1 - 2003/5/6
N2 - 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.
AB - 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.
KW - Immunotherapy
KW - Multicentre phase II study
KW - Renal cell carcinoma
UR - http://www.scopus.com/inward/record.url?scp=0037809210&partnerID=8YFLogxK
U2 - 10.1038/sj.bjc.6600915
DO - 10.1038/sj.bjc.6600915
M3 - Article
C2 - 12778059
AN - SCOPUS:0037809210
SN - 0007-0920
VL - 88
SP - 1346
EP - 1351
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 9
ER -