Platelet microparticles (PMP): A predictive factor of overall survival in hormone-refractory prostate cancer (HRPC) patients treated by chemotherapy

Abstract

4639 Background: Several studies suggest a causal relationship between platelets activation and cancer metastasis. Activated platelets release PMP, VEGF (vascular endothelial growth factor) and bFGF (basic fibroblast growth factor) which could play a role in patient outcome. Methods: Eligible chemonaive HRPC patients (pts) were required to have: ECOG performance status (PS) ≤2, progressive disease after antiandrogen withdrawal. Before chemotherapy, we quantified PMP in whole blood by flow cytometry using an anti-CD41 monoclonal antibody and plasmatic VEGF and bFGF by ELISA. As primary endpoint, we prospectively evaluated the impact of PMP on overall survival (OS) by Cox regression and log-rank test. Secondary, we studied the correlation between PMP and platelets, and their relationship with OS, incorporating an interaction term in the modelling (PMP and platelets). Results: Between July 2001 and April 2004, thirty-eight HRPC pts were treated by chemotherapy [docetaxel (92%), mitoxantrone (8%)] in our center. Median age was 69 years, with median values of hemoglobin 125 g/L, baseline prostate-specific antigen (PSA) 37.7 ng/mL, PMP 6 867 per μL, VEGF 18.1 pg/mL and bFGF 2.8 pg/mL. Significant correlations were observed between PMP and ECOG PS, hormone-sensitivity duration, Gleason and platelets. Median OS was significantly lower in pts with high PMP values (>6 788 per μL), compared to low PMP pts: 16.7 months (95% CI, 5.1–28.2) vs 25.2 months (95% CI, 20.2–30.3), P = 0.025, log-rank. Univariate analysis by Cox regression showed a significant relationship between OS and PMP level [HR = 0.41 (95% CI, 0.19–0.92), P = 0.04]. PMP kept their significance after adjusting by multivariate analysis for baseline hemoglobin, number of metastatic sites, and PSA doubling-time [HR = 0.37 (95% CI, 0.16–0.87), P = 0.02)]. An interaction term (PMP and platelets) was also predictive on OS (P = 0.01). Conclusions: PMP and their interaction with platelets were a predictive factor of OS in HRPC pts. Our analysis showed that the dynamic interaction between PMP and platelets has a major impact on outcome of HRPC pts. No significant financial relationships to disclose.