Kayak808,
First I would like repost Abstract #4650 from your link:
" Abstract #4650:
Correlation of Increased Eosinophil Count Following Sipuleucel-T Treatment with Outcome in Patients (pts) with Metastatic Castrate-Resistant Prostate Cancer (mCRPC)This exploratory analysis assessed the potential correlation between increased eosinophils (white blood cells), and overall survival, prostate cancer-specific survival, and immune response following treatment with PROVENGE. Data from three Phase 3 trials in patients with mCRPC (Studies D9901, D9902A, and IMPACT) were evaluated and the analysis included complete blood counts performed at baseline and at weeks 2-34 following treatment with PROVENGE.
In patients who were treated with PROVENGE, an increase in eosinophil counts were observed by week 6 and decreased to nearly baseline by week 14, while the eosinophil counts in the control arm remained consistent. Of the 377 patients treated with PROVENGE and eligible for analysis, 105 (27.9%) had eosinophilia. Baseline disease characteristics associated with eosinophilia were indicative of better prognosis (i.e., longer Halabi predicted survival [P=0.007], lower PSA [P=0.033], higher Hgb [P < 0.001], and no prior docetaxel [P=0.012]). In univariate analyses, eosinophilia correlated with improved overall survival (HR=0.75; 95%CI: 0.56—1.01; P=0.057) and prostate cancer-specific survival (HR=0.71; 95%CI: 0.53—0.97; P=0.031). The magnitude of eosinophilia positively correlated with antigen-specific humoral responses (P ≤0.039 for wks 6, 14 and 26) and elevations in the cytokines at wk 6 (IL2 [P=0.011], IL5 [P=0.038] and TARC [P=0.001]). AEs occurring more frequently (P < 0.05) in pts with eosinophilia were infusion-related: pyrexia (33.3 v 21.3%) and nausea (19.0 v 10.7%). No cases of hypereosinophilic syndrome were reported.
The analysis suggests that increases in eosinophils after treatment with PROVENGE correlated with improved overall survival and prostate cancer-specific survival. Larger increases in eosinophil counts were associated with humoral responses and Th2-type cytokine production. The analysis supports further studies to evaluate eosinophilia measurement as a potential biomarker for PROVENGE response.
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These study findings are interesting and suggest that looking at eosinophil count could give insight into how a patient may respond to treatment with PROVENGE," said Douglas McNeel, MD, University of Wisconsin, Madison. "
We can see the specific responses as to possibly why and which patients are likely to respond and benefit from Provenge. It can give more insight in these crucial areas who best responds and why . I hope enough pieces of the puzzle come together to better explain Provenge to the medical community and patients regarding most beneficial time to treat, continue identifying patients most likely to respond .
Eosinophils can act as antigen presenting cells (like dendritic cells) in relation to bacterial infection. Bottom line:the association of an elevated level of Eosinophils and better survival after a Provenge treatment could mean that Provenge has somehow elicited this potent immune effect against cancer cells beyond just the activities of the dendritic cells. There is more going on in that cocktail of activated cells than we understand yet: antigen spread?
Douglas McNeel, MD, PhD also said:
"An increased count of eosinophil granulocytes— a type of white blood cell that becomes active when a patient has certain medical conditions or allergic reactions—could serve as a biomarker to determine response to sipuleucel- T. A retrospective analysis of data from three studies (D9901, D9902A, and IMPACT) found that increased eosinophil counts were seen in patients who received sipuleucel-T by their sixth week of treatment. Those levels returned to near baseline by week 14 of the treatment. Patients with eosinophilia had better prostate cancer–specific survival (hazard ratio [HR] = 0.713; 95% CI, 0.525-0.970; P = .031) and better overall survival (HR = 0.753; 95% CI, 0.563- 1.008; P = .057) than patients without eosinophilia."www.onclive.com/publications/obtn/2012/July-2012/Sipuleucel-T-Studies-Support-Earlier-Use-Reveal-Potential-BiomarkerFor most other therapies tumor progression is the clear signal in practice, regardless of the preference for survival. Now it looks as though there is a way to monitor the effectiveness of Provenge.
You maybe will be interesting review also this work:
"Sipuleucel-T immune parameters correlate with survival: an analysis of the randomized phase 3 clinical trials in men with castration-resistant prostate cancerNadeem A. Sheikh , Daniel Petrylak, Philip W. Kantoff, Corazon dela Rosa, Frances P. Stewart, Ling-Yu Kuan, James B. Whitmore, James B. Trager, Christian H. Poehlein, Mark W. Frohlich and David L. Urdal
Received: 22 March 2012Accepted: 5 July 2012Published online: 3 August 2012"
link.springer.com/article/10.1007%2Fs00262-012-1317-2/fulltext.html My best, Hope