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Kirkwood JM , Lee S , Moschos S , Albertini MR , Michalak JC , Sander C , Whiteside T , Butterfield LH , Weiner L
Immunogenicity and Antitumor Effects of Vaccination with Peptide Vaccine +/- Granulocyte-Monocyte Colony-Stimulating Factor and/or IFN-alpha 2b in Advanced Metastatic Melanoma: Eastern Cooperative Oncology Group Phase II Trial E1696
Clinical Cancer Research. 2009 Feb;15(4) :1443-1451
PMID: ISI:000263592600039    PMCID: PMC2769898   
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Purpose: No therapy has ever shown prolongation of survival in stage IV metastatic melanoma. The association of cytokine-induced autoimmunity with improved prognosis led us to investigate the effect of multi-epitope melanoma vaccines alone and in combination with cytokines in this Eastern Cooperative Oncology Group multicenter phase II trial. Experimental Design: Eligible patients were required to have failed prior therapies and to be HLA-A2 positive. Three HLA class I-restricted lineage antigen epitopes were administered in a factorial 2 x 2 design. Peptide vaccine alone (arm A), or combined with granulocytemonocyte colony-stimulating factor (GM-CSF; Immunex) 250 mu g/d subcutaneously for 14 of 28 days each month (arm 13), or combined with IFN-alpha 2b (Intron A; Schering-Plough) 10 million units/m(2) three times a week (arm C), or combined with both IFN-alpha 2b and GM-CSF (arm D). The primary endpoint was immune response measured by enzyme-linked immunospot assay; secondary endpoints were clinical antitumor response, disease-free survival, and overall survival. Results: One hundred twenty patients enrolled and 115 patients were analyzed. Immune responses to at least one melanoma antigen were observed in 26 of 75 (35%) patients with serial samples. Neither IFN-alpha 2b nor GM-CSF significantly improved immune responses. Six objective clinical responses were documented. At a median follow-up of 25.4 months, the median overall survival of patients with vaccine immune response was significantly longer than that of patients with no immune response (21.3 versus 13.4 months; P = 0.046). Conclusion: Immune response to vaccination correlates with prolonged survival in patients with metastatic melanoma and is not enhanced by immunomodulatory cytokines as tested in this
Kirkwood, John M. Lee, Sandra Moschos, Stergios Albertini, Mark R. Michalak, John C. Sander, Cindy Whiteside, Theresa Butterfield, Lisa H. Weiner, Louis 41 AMER ASSOC CANCER RESEARCH; 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA 410QI