Unclassified Pleomorphic and Spindle Cell Pulmonary Neoplasm with Brain Metastases after Prasugrel

Heart Drug™ Research Laboratories, Johns Hopkins University, Towson, Md., USA.
Cardiology (Impact Factor: 2.18). 01/2013; 124(2):85-90. DOI: 10.1159/000346382
Source: PubMed


There was an excess of new solid neoplasms (112 vs. 69), and cancer deaths (24 vs. 15) after prasugrel in the TRITON (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition). These cancers usually occur after 4 months following prasugrel, and women are especially at risk. The hypothesis has been offered that prasugrel, but not aspirin or clopidogrel, causes indirect modulation of tumor growth, and/or enhanced metastatic dissemination due to instability of platelet-tumor cell aggregates via the inability to keep cancer locally within the platelet thrombi due to excessive chronic platelet inhibition.

Case report:
A 70-year old female diabetic patient underwent drug-eluting stent implantation. The patient received a loading dose of prasugrel (60 mg), followed by prasugrel 10 mg/daily as well as aspirin (81 mg/daily). After 4 months on dual antiplatelet therapy she expectorated blood when coughing. A lung X-ray and CT scan revealed numerous lung nodules later diagnosed as unclassified pleomorphic and spindle cell malignant solid neoplasm. The patient died following multiple brain metastasis.

Female gender, duration of prasugrel exposure, rare unclassified neoplasm pathology type and a tumor of a highly metastatic and aggressive nature in the index patient should be regarded with caution. The effects of novel antiplatelet agents on the onset of cancer should be tested in future mega-trials.

25 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: Platelets play a crucial role in the pathophysiological processes of hemostasis and thrombosis. Increasing evidence indicates that they fulfill much broader roles in balancing health and disease. The presence of tumor cells affects platelets both numerically, through a wide variety of mediators and cytokines, or functionally through tumor cell-induced platelet activation, the first step toward cancer-induced thrombosis. This induction results from signaling events through the different platelet receptors, or may be cytokine-mediated. Reciprocally, upon activation, the platelets will release a myriad of growth factors from their dense and α-granules and peroxisomes; these will directly impact tumor growth, tethering, and spread. A similar cross-talk is initiated between tumor microvesicles stimulating the platelets and platelet microparticles, promoting both thrombosis and tumor growth. A vicious loop of activation thereafter takes place. Platelets directly and indirectly promote tumor growth, and enable a molecular mimicry coating the malignant growth and allowing metastasizing cells to escape T-cell-mediated immunity and natural killer cell surveillance. Breaking this vicious activation loop with nonspecific platelet inhibitors, such as aspirin, or by targeting specific sites on the activation cascade may offer a mean to reduce both the risks of development and progression of cancer and the risk of thrombosis.
    Seminars in Thrombosis and Hemostasis 03/2014; 40(3). DOI:10.1055/s-0034-1370767 · 3.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Ischemic heart disease is the primary cause of death worldwide. The pathophysiological process of cardiovascular diseases is linked to atheromatous plaque formation, while plaque rupture releases thrombogenic elements, which lead to activation of platelets, blood clotting and formation of thrombi. Platelet inhibitors are used to prevent thrombosis. The present systematic review discusses the efficacy of prasugrel in terms of platelet inhibition potential and clinical prevention of cardiovascular outcomes. The balance between reduction of ischemic events as a measure of drug efficacy and the risk of bleeding is reviewed. Other adverse events observed in patients treated with this platelet inhibitor are discussed, including hematological complications, and cutaneous and hepatic idiosyncratic reactions. The complex relationship between prasugrel use and cancer promotion is also described.
    Clinical biochemistry 03/2014; 47(7-8). DOI:10.1016/j.clinbiochem.2014.03.005 · 2.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The impact of antithrombotics on cancer is currently under intense investigation because of the excess of solid cancers in trials after thienopyridines such as TRITON (prasugrel), DAPT (prasugrel and clopidogrel), PAR-1 thrombin antagonist in TRACER (vorapaxar), pyrimidines in PEGASUS (ticagrelor), and in APPRAISE-2 after apixaban. However, whether patient survival after solid cancer (SASC) in antithrombotic trials may be affected is unknown. We matched the 1-year SASC rate in antithrombotic trials reported by Food and Drug Administration with the census averages in Surveillance, Epidemiology, and End Results (SEER) Program by the US National Cancer Institute and World Health Organization (WHO) surveys. The Food and Drug Administration provided the SASC data for 3 trials with similar cancer survival of about 70% for the first year of follow-up in TRITON, APPRAISE-2, and ARISTOTEL. Adjusted cancers in TRITON with SEER (odds ratio 0.92; 95% confidence interval 0.53 to 1.59, p = 0.4351) and WHO (odds ratio 0.99; 95% confidence interval 0.57 to 1.7, p = 1.00) revealed very close if not identical SASC rates in antithrombotic trials compared to epidemiologic census estimates. In conclusion, SASC rates in patients enrolled in antithrombotic trials do not differ from SEER or World Health Organization averages. Copyright © 2015 Elsevier Inc. All rights reserved.
    The American Journal of Cardiology 06/2015; 116(6). DOI:10.1016/j.amjcard.2015.06.026 · 3.28 Impact Factor