Limits...
Cardiotoxicity of anticancer drugs: the need for cardio-oncology and cardio-oncological prevention.

Albini A, Pennesi G, Donatelli F, Cammarota R, De Flora S, Noonan DM - J. Natl. Cancer Inst. (2009)

Bottom Line: In the past, cardiotoxic risk was less evident, but it is increasingly an issue, particularly with combination therapy and adjuvant therapy.Today's oncologists must be fully aware of cardiovascular risks to avoid or prevent adverse cardiovascular effects, and cardiologists must now be ready to assist oncologists by performing evaluations relevant to the choice of therapy.There is a need for cooperation between these two areas and for the development of a novel discipline, which could be termed cardio-oncology or onco-cardiology.

View Article: PubMed Central - PubMed

Affiliation: Oncology Research Division, MultiMedica Castellanza (VA), Milan, Italy. adriana.albini@multimedica.it

ABSTRACT
Due to the aging of the populations of developed countries and a common occurrence of risk factors, it is increasingly probable that a patient may have both cancer and cardiovascular disease. In addition, cytotoxic agents and targeted therapies used to treat cancer, including classic chemotherapeutic agents, monoclonal antibodies that target tyrosine kinase receptors, small molecule tyrosine kinase inhibitors, and even antiangiogenic drugs and chemoprevention agents such as cyclooxygenase-2 inhibitors, all affect the cardiovascular system. One of the reasons is that many agents reach targets in the microenvironment and do not affect only the tumor. Combination therapy often amplifies cardiotoxicity, and radiotherapy can also cause heart problems, particularly when combined with chemotherapy. In the past, cardiotoxic risk was less evident, but it is increasingly an issue, particularly with combination therapy and adjuvant therapy. Today's oncologists must be fully aware of cardiovascular risks to avoid or prevent adverse cardiovascular effects, and cardiologists must now be ready to assist oncologists by performing evaluations relevant to the choice of therapy. There is a need for cooperation between these two areas and for the development of a novel discipline, which could be termed cardio-oncology or onco-cardiology. Here, we summarize the potential cardiovascular toxicities for a range of cancer chemotherapeutic and chemopreventive agents and emphasize the importance of evaluating cardiovascular risk when patients enter into trials and the need to develop guidelines that include collateral effects on the cardiovascular system. We also discuss mechanistic pathways and describe several potential protective agents that could be administered to patients with occult or overt risk for cardiovascular complications.

Show MeSH

Related in: MedlinePlus

Examples of major mechanisms causing cardiotoxicity of anticancer treatments (black text), clinically used therapeutic agents (green text), and potential protective agents (blue cursive text). ROS = reactive oxygen species; ACE = angiotensin-converting enzyme, NSAIDs = nonsteroidal anti-inflammatory drugs.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2802286&req=5

fig3: Examples of major mechanisms causing cardiotoxicity of anticancer treatments (black text), clinically used therapeutic agents (green text), and potential protective agents (blue cursive text). ROS = reactive oxygen species; ACE = angiotensin-converting enzyme, NSAIDs = nonsteroidal anti-inflammatory drugs.

Mentions: Moving toward a protective chemoprevention approach, several drugs may be useful to flank chemotherapy to reduce cardiotoxicity without losing antitumor activity, and possibly even to enhance antitumor activity (Figure 3). Most of these approaches are still experimental; however, some could easily be considered for clinical trials. Dexrazoxane, a cyclic derivative of EDTA that chelates iron and thereby prevents the generation of cardiotoxic reactive oxygen species, is a drug used to protect the myocardium from anthracycline-induced cardiotoxicity (89). At high concentrations, dexrazoxane also inhibits topoisomerase II, which may also be involved in its cardioprotective activities (89). Data from nine clinical studies that had enrolled a total of 1403 patients who received anthracycline-based therapy for advanced breast cancer showed an overall benefit from dexrazoxane in protecting cancer patients from anthracycline-induced HF (90). However, this drug may increase the risk of adverse effects, such as a slightly higher incidence of myelosuppression, infection, and fever. An early dropout rate was also higher in patients who received dexrazoxane (91).


Cardiotoxicity of anticancer drugs: the need for cardio-oncology and cardio-oncological prevention.

Albini A, Pennesi G, Donatelli F, Cammarota R, De Flora S, Noonan DM - J. Natl. Cancer Inst. (2009)

Examples of major mechanisms causing cardiotoxicity of anticancer treatments (black text), clinically used therapeutic agents (green text), and potential protective agents (blue cursive text). ROS = reactive oxygen species; ACE = angiotensin-converting enzyme, NSAIDs = nonsteroidal anti-inflammatory drugs.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2802286&req=5

fig3: Examples of major mechanisms causing cardiotoxicity of anticancer treatments (black text), clinically used therapeutic agents (green text), and potential protective agents (blue cursive text). ROS = reactive oxygen species; ACE = angiotensin-converting enzyme, NSAIDs = nonsteroidal anti-inflammatory drugs.
Mentions: Moving toward a protective chemoprevention approach, several drugs may be useful to flank chemotherapy to reduce cardiotoxicity without losing antitumor activity, and possibly even to enhance antitumor activity (Figure 3). Most of these approaches are still experimental; however, some could easily be considered for clinical trials. Dexrazoxane, a cyclic derivative of EDTA that chelates iron and thereby prevents the generation of cardiotoxic reactive oxygen species, is a drug used to protect the myocardium from anthracycline-induced cardiotoxicity (89). At high concentrations, dexrazoxane also inhibits topoisomerase II, which may also be involved in its cardioprotective activities (89). Data from nine clinical studies that had enrolled a total of 1403 patients who received anthracycline-based therapy for advanced breast cancer showed an overall benefit from dexrazoxane in protecting cancer patients from anthracycline-induced HF (90). However, this drug may increase the risk of adverse effects, such as a slightly higher incidence of myelosuppression, infection, and fever. An early dropout rate was also higher in patients who received dexrazoxane (91).

Bottom Line: In the past, cardiotoxic risk was less evident, but it is increasingly an issue, particularly with combination therapy and adjuvant therapy.Today's oncologists must be fully aware of cardiovascular risks to avoid or prevent adverse cardiovascular effects, and cardiologists must now be ready to assist oncologists by performing evaluations relevant to the choice of therapy.There is a need for cooperation between these two areas and for the development of a novel discipline, which could be termed cardio-oncology or onco-cardiology.

View Article: PubMed Central - PubMed

Affiliation: Oncology Research Division, MultiMedica Castellanza (VA), Milan, Italy. adriana.albini@multimedica.it

ABSTRACT
Due to the aging of the populations of developed countries and a common occurrence of risk factors, it is increasingly probable that a patient may have both cancer and cardiovascular disease. In addition, cytotoxic agents and targeted therapies used to treat cancer, including classic chemotherapeutic agents, monoclonal antibodies that target tyrosine kinase receptors, small molecule tyrosine kinase inhibitors, and even antiangiogenic drugs and chemoprevention agents such as cyclooxygenase-2 inhibitors, all affect the cardiovascular system. One of the reasons is that many agents reach targets in the microenvironment and do not affect only the tumor. Combination therapy often amplifies cardiotoxicity, and radiotherapy can also cause heart problems, particularly when combined with chemotherapy. In the past, cardiotoxic risk was less evident, but it is increasingly an issue, particularly with combination therapy and adjuvant therapy. Today's oncologists must be fully aware of cardiovascular risks to avoid or prevent adverse cardiovascular effects, and cardiologists must now be ready to assist oncologists by performing evaluations relevant to the choice of therapy. There is a need for cooperation between these two areas and for the development of a novel discipline, which could be termed cardio-oncology or onco-cardiology. Here, we summarize the potential cardiovascular toxicities for a range of cancer chemotherapeutic and chemopreventive agents and emphasize the importance of evaluating cardiovascular risk when patients enter into trials and the need to develop guidelines that include collateral effects on the cardiovascular system. We also discuss mechanistic pathways and describe several potential protective agents that could be administered to patients with occult or overt risk for cardiovascular complications.

Show MeSH
Related in: MedlinePlus