Data from Differential Platelet Levels Affect Response to Taxane-Based Therapy in Ovarian Cancer

Abstract

<div>Abstract<p><b>Purpose:</b> We hypothesized that platelet levels during therapy could serve as a biomarker for response to therapy and that manipulation of platelet levels could impact responsiveness to chemotherapy.</p><p><b>Experimental Design:</b> The medical records of patients with recurrent or progressive ovarian cancer were retrospectively queried for changes in platelet and CA-125 levels during primary therapy. <i>In vitro</i> coculture experiments and <i>in vivo</i> orthotopic models of human ovarian cancer in mice were used to test the effect of modulating platelet levels on tumor growth and responsiveness to docetaxel.</p><p><b>Results:</b> Thrombocytosis at the diagnosis of ovarian cancer was correlated with decreased interval to progression (<i>P</i> = 0.05) and median overall survival (<i>P</i> = 0.007). Mean platelet levels corrected during primary therapy and rose at recurrence. Contrary to treatment-responsive patients, in a cohort of patients refractory to primary therapy, platelet levels did not normalize during therapy. In A2780, HeyA8, and SKOV3-ip1 ovarian cancer cell lines, platelet coculture protected against apoptosis (<i>P</i> < 0.05). In orthotopic models of human ovarian cancer, platelet depletion resulted in 70% reduced mean tumor weight (<i>P</i> < 0.05). Compared with mice treated with docetaxel, mice treated with both docetaxel and platelet-depleting antibody had a 62% decrease in mean tumor weight (<i>P</i> = 0.04). Platelet transfusion increased mean aggregate tumor weight 2.4-fold (<i>P</i> < 0.05), blocked the effect of docetaxel on tumor growth (<i>P</i> = 0.55) and decreased tumor cell apoptosis. Pretransfusion aspirinization of the platelets blocked the growth-promoting effects of transfusion.</p><p><b>Conclusions:</b> Platelet-driven effects of chemotherapy response may explain clinical observations. <i>Clin Cancer Res; 21(3); 602–10. ©2014 AACR.</i></p></div>