Abstract
The purpose of the study was to determine toxicity, efficacy and immunologic effects of concurrent subcutaneous injections of lowdose
interleukin-2 (LD-IL-2), granulocyte–monocyte colony-stimulating factor (GM-CSF) and interferon-a 2b (IFNa) 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 mIUm2), GM-CSF (2.5 mg kg1) and IFNa (5 mIU flat1) 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 mIUm2 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 CD4þHLA-DRþ cells correlated with response. Pretreatment number of CD4þHLA-DRþ cells and postimmunotherapy levels of lymphocytes, CD3þ, CD4þ and CD8þ T cells, but not of NK or B cells, correlated with prolonged survival. Immunotherapy with concurrent subcutaneous GM-CSF, LD-IL-2 and IFNa 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.
interleukin-2 (LD-IL-2), granulocyte–monocyte colony-stimulating factor (GM-CSF) and interferon-a 2b (IFNa) 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 mIUm2), GM-CSF (2.5 mg kg1) and IFNa (5 mIU flat1) 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 mIUm2 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 CD4þHLA-DRþ cells correlated with response. Pretreatment number of CD4þHLA-DRþ cells and postimmunotherapy levels of lymphocytes, CD3þ, CD4þ and CD8þ T cells, but not of NK or B cells, correlated with prolonged survival. Immunotherapy with concurrent subcutaneous GM-CSF, LD-IL-2 and IFNa 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.
| Original language | English |
|---|---|
| Article number | DOI: 10.1038/sj.bjc.6600915 |
| Pages (from-to) | 1346-1351 |
| Number of pages | 6 |
| Journal | British Journal of Cancer |
| Volume | 2003: 88 |
| Publication status | Published - 6 May 2003 |