Platelet microparticles: a potential predictive factor of survival in hormone-refractory prostate cancer patients treated with docetaxel-based chemotherapy.

摘要

BACKGROUND: Several studies suggest a causal relationship between platelet activation and cancer metastasis. Activated platelet microparticles (PMPs) release vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), which play a major role in angiogenesis. OBJECTIVE: We conducted a prospective, nonrandomised, single-centre study in hormone-refractory prostate cancer (HRPC) patients to determine the impact of PMPs on the outcome. DESIGN, SETTING, AND PARTICIPANTS: Eligible chemonaive and metastatic HRPC patients received docetaxel-based chemotherapy and a low dose of prednisone. INTERVENTION: PMPs in whole blood were quantified before the start of chemotherapy through flow cytometry using an anti-CD41a monoclonal antibody, and plasma VEGF and bFGF were determined with an enzyme-linked immunosorbent assay. MEASUREMENTS: The primary end point was to evaluate the impact of the PMPs on overall survival (OS). We also studied the statistical interaction between PMPs and platelets and their relationship with OS. The median PMP value was used to sort patients into two groups. RESULTS AND LIMITATIONS: Data of 43 consecutive HRPC patients treated in a single French centre were analysed. Significant correlations were observed between Eastern Cooperative Oncology Group performance status (ECOG PS), platelets, and PMP level. The median OS was significantly shorter for patients with >6867 PMPs per microl of whole blood than for those with lower values (16.7 vs 26.4 mo, p=0.013). A significant relationship was found between OS and PMPs, whereas a statistical interaction term between PMPs and platelets was significantly associated with OS (p=0.019). No association was found between OS and plasma VEGF and bFGF. In the multivariate analysis, only baseline prostate-specific antigen (PSA) and ECOG PS remained significantly predictive of risk of death. CONCLUSIONS: In HRPC patients, PMPs and their interaction with platelets were predictive of outcome. A biologic association between PMPs and the OS of HRPC patients, independent of chemotherapy regimen, should be demonstrated by confirmatory prospective studies.