Therapy Insight: Management of cardiovascular disease in patients with cancer and cardiac complications of cancer therapy
ABSTRACT Cardiac disease in patients with cancer or caused by cancer therapy is a clinical problem of emerging importance. Optimum management of cardiovascular disease can mean that patients with cancer can successfully receive therapies to treat their malignancy and can reduce morbidity and mortality due to cardiovascular disease in cancer survivors. The presence of cancer and cancer-related morbidities substantially complicates the management of cardiovascular disease in cancer patients. In this Review, we discuss management strategies for cardiovascular disease in patients with cancer, focusing on the prevention and treatment of congestive heart failure and myocardial infarction.
- SourceAvailable from: Ramon Kaneno
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- "The dose-delivery schedule of conventional chemotherapy, which determines its efficacy and toxicity, is based on the maximum tolerated dose (MTD), i.e. the highest dose of a drug that does not cause unacceptable side effects. This strategy of MTD chemotherapy has lead to cure and disease control in a significant number of patients but is associated with significant short-term and long-term toxicity and complications, including myelosuppression, neutropenia, trombocytopenia, increased risk of infection and bleeding, gastrointestinal dysfunctions, arthralgia, liver toxicity, and the cardiac and nervous system damage [4-6]. "
ABSTRACT: The dose-delivery schedule of conventional chemotherapy, which determines its efficacy and toxicity, is based on the maximum tolerated dose. This strategy has lead to cure and disease control in a significant number of patients but is associated with significant short-term and long-term toxicity. Recent data demonstrate that moderately low-dose chemotherapy may be efficiently combined with immunotherapy, particularly with dendritic cell (DC) vaccines, to improve the overall therapeutic efficacy. However, the direct effects of low and ultra-low concentrations on DCs are still unknown. Here we characterized the effects of low noncytotoxic concentrations of different classes of chemotherapeutic agents on human DCs in vitro. DCs treated with antimicrotubule agents vincristine, vinblastine, and paclitaxel or with antimetabolites 5-aza-2-deoxycytidine and methotrexate, showed increased expression of CD83 and CD40 molecules. Expression of CD80 on DCs was also stimulated by vinblastine, paclitaxel, azacytidine, methotrexate, and mitomycin C used in low nontoxic concentrations. Furthermore, 5-aza-2-deoxycytidine, methotrexate, and mitomycin C increased the ability of human DCs to stimulate proliferation of allogeneic T lymphocytes. Thus, our data demonstrate for the first time that in low noncytotoxic concentrations chemotherapeutic agents do not induce apoptosis of DCs, but directly enhance DC maturation and function. This suggests that modulation of human DCs by noncytotoxic concentrations of antineoplastic drugs, i.e. chemomodulation, might represent a novel approach for up-regulation of functional activity of resident DCs in the tumor microenvironment or improving the efficacy of DCs prepared ex vivo for subsequent vaccinations.Journal of Translational Medicine 02/2009; 7(1):58. DOI:10.1186/1479-5876-7-58 · 3.93 Impact Factor
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ABSTRACT: The cancer patient with coronary disease presents particular challenges that directly impact on the management of coronary disease, both stable and acute. The frequent need for surgery in the cancer patient is an important consideration in avoiding a coronary artery stent or any percutaneous coronary intervention for management of chronic stable angina, which will delay surgery or pose of risk of stent thrombosis during surgery. Cancer surgery is considered low or intermediate cardiac risk so revascularization before surgery is needed only in exceptional circumstances. Medical treatment in most patients or coronary artery bypass graft in high risk situations may be preferable if the cancer is being actively treated. The likelihood of thrombocytopenia, either primary from bone marrow disease, or secondarily during chemotherapy causes concern about the need for continuous use of platelet suppressing agents, aspirin for all patients, or double antiplatelet therapy in all patients after receiving a coronary artery stent. Drug-eluting stents pose special problems and should be avoided. Even bare metal stents may have a higher long-term risk of stent thrombosis in the cancer patient. The increase in propensity for venous clotting, either as a result of the cancer itself, or especially with selected chemotherapeutic agents may be an issue after stenting and certainly early after coronary bypass surgery. Aggressive medical treatment to reduce risk factors, especially with statins is essential to stabilize the underlying coronary disease.Progress in cardiovascular diseases 09/2010; 53(2):149-56. DOI:10.1016/j.pcad.2010.06.004 · 4.25 Impact Factor
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ABSTRACT: Doxorubicin (DOX) is a widely used anticancer drug for solid tumors and hematologic malignancy, but its active use is hampered by serious adverse effects, including thrombocytopenia. Although bone marrow toxicity of DOX has been suggested to be the sole mechanism underlying the reduced platelet counts, the direct effects of DOX on platelets have never been examined. Here, we investigated the DOX-induced platelet cytotoxicity and its underlying mechanism in an effort to elucidate the contribution of platelet cytotoxicity to DOX-induced thrombocytopenia. In freshly isolated human platelets, DOX induced platelet cytotoxicity in a time-dependent and concentration-dependent manner. Reactive oxygen species (ROS) generation, decreased glutathione levels and subsequent protein thiol depletion were shown to underlie the DOX-induced platelet cytotoxicity. Conspicuously, DOX-treated platelets displayed apoptotic features such as caspase-3 activation, reduced mitochondrial transmembrane potential, and phosphatidylserine exposure. Decreased glutathiolation of procaspase-3 was shown to be a link between protein thiol depletion and caspase-3 activation. It is of note that DOX-mediated platelet cytotoxicity was significantly enhanced by shear stress, a common complicating factor in cancer patients. These in vitro results were further confirmed by an in vivo animal model, where administration of DOX induced a platelet count decrease, ROS generation, caspase-3 activation, protein thiol depletion, and damaged platelet integrity. We demonstrated that DOX can directly induce platelet cytotoxicity through ROS generation, decreased glutathione levels, and protein thiol depletion. We believe that this study provides important evidence for the role of DOX-induced platelet cytotoxicity in the development of thrombocytopenia in DOX-treated patients.Journal of Thrombosis and Haemostasis 06/2009; 7(7):1172-83. DOI:10.1111/j.1538-7836.2009.03477.x · 5.72 Impact Factor