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

多西紫杉醇 医学 卵巢癌 血小板 内科学 化疗 癌症 紫杉烷 血小板增多症 肿瘤科 血小板输注 胃肠病学 免疫学 乳腺癌
作者
Justin Bottsford-Miller,Hyun Jin Choi,Heather J. Dalton,Rebecca L. Stone,Min Soon Cho,Monika Haemmerle,Alpa M. Nick,Sunila Pradeep,Behrouz Zand,Rebecca A. Previs,Chad V. Pecot,Erin K. Crane,Wei Hu,Susan K. Lutgendorf,Vahid Afshar‐Kharghan,Anil K. Sood
出处
期刊:Clinical Cancer Research [American Association for Cancer Research]
卷期号:21 (3): 602-610 被引量:79
标识
DOI:10.1158/1078-0432.ccr-14-0870
摘要

Abstract Purpose: 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. Experimental Design: 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. In vitro coculture experiments and in vivo 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. Results: Thrombocytosis at the diagnosis of ovarian cancer was correlated with decreased interval to progression (P = 0.05) and median overall survival (P = 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 (P < 0.05). In orthotopic models of human ovarian cancer, platelet depletion resulted in 70% reduced mean tumor weight (P < 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 (P = 0.04). Platelet transfusion increased mean aggregate tumor weight 2.4-fold (P < 0.05), blocked the effect of docetaxel on tumor growth (P = 0.55) and decreased tumor cell apoptosis. Pretransfusion aspirinization of the platelets blocked the growth-promoting effects of transfusion. Conclusions: Platelet-driven effects of chemotherapy response may explain clinical observations. Clin Cancer Res; 21(3); 602–10. ©2014 AACR.
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