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

Verra N, Jansen R, Groenewegen G, Mallo H, Kersten MJ, Bex A, Vyth-Dreese FA, Sein J, van de Kasteele W, Nooijen WJ, de Waal M, Horenblas S, de Gast GC - Br. J. Cancer (2003)

Bottom Line: 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.Response and survival with this form of immunotherapy seem to be more dependent on expansion/activation of T cells than of NK cells.

View Article: PubMed Central - PubMed

Affiliation: Division of Immunology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.

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-alpha 2b (IFNalpha) 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 mIU m(-2)), GM-CSF (2.5 microg kg(-1)) and IFNalpha (5 mIU 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 mIU 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, 1PR) 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 IFNalpha 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 of T cells than of NK cells.

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Median survival for all 63 registered patients was 9.5 months
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fig1: Median survival for all 63 registered patients was 9.5 months

Mentions: Of the 25 patients with synchronic metastases, only 14 underwent nephrectomy and 11 patients underwent no nephrectomy, because of rapidly progressive disease ( Table 2). Two patients achieved CR after nephrectomy, of whom one got a relapse of his lung and pleural lesions after 4 months and one is still in continued CR for 15+ months. One patient with lung and adrenal metastasis achieved a PR. The response rate in the whole group was 11 out of 59 (19%) with five CR and six PR. Three of the five CR patients are in maintained remission (15+, 40+, 40+ months). Survival of all patients entering the study (n=63) is shown in Figure 1Figure 1


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

Verra N, Jansen R, Groenewegen G, Mallo H, Kersten MJ, Bex A, Vyth-Dreese FA, Sein J, van de Kasteele W, Nooijen WJ, de Waal M, Horenblas S, de Gast GC - Br. J. Cancer (2003)

Median survival for all 63 registered patients was 9.5 months
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2741048&req=5

fig1: Median survival for all 63 registered patients was 9.5 months
Mentions: Of the 25 patients with synchronic metastases, only 14 underwent nephrectomy and 11 patients underwent no nephrectomy, because of rapidly progressive disease ( Table 2). Two patients achieved CR after nephrectomy, of whom one got a relapse of his lung and pleural lesions after 4 months and one is still in continued CR for 15+ months. One patient with lung and adrenal metastasis achieved a PR. The response rate in the whole group was 11 out of 59 (19%) with five CR and six PR. Three of the five CR patients are in maintained remission (15+, 40+, 40+ months). Survival of all patients entering the study (n=63) is shown in Figure 1Figure 1

Bottom Line: 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.Response and survival with this form of immunotherapy seem to be more dependent on expansion/activation of T cells than of NK cells.

View Article: PubMed Central - PubMed

Affiliation: Division of Immunology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.

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-alpha 2b (IFNalpha) 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 mIU m(-2)), GM-CSF (2.5 microg kg(-1)) and IFNalpha (5 mIU 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 mIU 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, 1PR) 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 IFNalpha 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 of T cells than of NK cells.

Show MeSH
Related in: MedlinePlus