Specifically they were interested in the short-term effect of docetaxel (doc) chemotherapy on serum levels of pro-inflammatory cytokines and correlate them with doc-induced apoptosis and clinical response in patients with castration-resistant (CRPC) and doc retreatment. They studied 78 patients with CRPC on doc retreatment. Blood samples were collected before and 2 days after doc. Multiplex immunoassays measured serum levels of 12 pro-inflammatory cytokines and ELISA (PEVIVA) measured tumor cell death (M65 and M30).
They found that Doc induced a significant increase in serum levels of pro-inflammatory cytokines 2 days after the first chemotherapy dose in both the first and second cycles. Macrophage inflammatory protein (MIP)-1a, MIP-1ß, Eotaxin, interferon-inducible (IP)-10 and tumor-necrosis factor (TNF)-α increased in both and transforming growth factor (TGF)-α in the first and interleukin (IL-6) and macrophage chemotactic protein (MCP-1) in the second series only. Tumor cell apoptosis increased significantly after doc in both cycles. In contrast, serum vascular endothelial growth factor (VEGF) decreased after doc in both cycles. Prior to the first chemotherapy cycle, both C-reactive protein (CRP) and IL-6 correlated with apoptosis and CRP with VEGF. In the second cycle, CRP and TGF-α correlated with necrosis. Epidermal growth factor (EGF), granulocyte-colony stimulating factor (G-CSF) on day 1 and IL-6 on day 3 were associated with maximum PSA response in the first, but not in the second cycle. M65, CRP, IL-6, IL-8 on day 1 and M30, M65, IL-6, TNF-a and VEGF on day 3 of the first cycle of the first series correlated with cancer-specific survival. They concluded that immediate expression of pro-inflammatory cytokines and VEGF suppression may result from docetaxel-induced tumor cell apoptosis. This may in turn support generation of effective anti-tumoral immune responses as apoptotic tumor cell death may improve antigen presentation and pro-inflammatory cytokines favoring recruitment of progenitor cells into tumor areas after docetaxel-induced tissue death.
Presented by G. Kramer, et al. at the 26th Annual European Association of Urology (EAU) Congress - March 18 - 21, 2011 - Austria Centre Vienna, Vienna, Austria