Given the increasing number of older patients with both cancer and cardiovascular disease and the potential cardiotoxic effects of many cancer therapies, creation of a new specialty called cardio-oncology or onco-cardiology has been suggested (Albini A, et al. J Natl Cancer Inst. 2010;102:14-25). New strategies for protecting against cardiotoxicity in patients treated with anthracyclines were reported at the American Heart Association Scientific Sessions 2009.
A study by researchers at the University of Cagliari in Cagliari, Italy, showed that the angiotensin II receptor blocker telmisartan can counteract the cardiotoxic effect of epirubicin, presumably by limiting inactivation of cardiac antioxidant defenses.
Using conventional echocardiography and tissue Doppler in previous studies, the researchers, led by Christian Cadeddu, MD, demonstrated impairment of left ventricular function at epirubicin doses as low as 200 mg/m2, even in the absence of changes in biochemical markers denoting oxidative stress. The researchers had also shown that free radicals and the reninangiotensin-aldosterone system play a role in the pathogenesis of epirubicin cardiotoxicity. Telmisartan limits the production of oxygen free radicals by inhibiting the activation of superoxide sources, such as nicotinamide adenine dinucleotide phosphate-oxidase, mitochondria, and xanthine oxidase.
In the present phase 2, placebo-controlled study, the authors investigated whether telmisartan could prevent preclinical myocardial damage induced by epirubicin. The trial enrolled 36 patients (26 women, 10 men; mean age, 56 years) who were free of cardiac disease, were previously untreated for a variety of solid tumors, and were to receive an epirubicin-based regimen. They were randomized to receive telmisartan 40 mg/day or placebo, starting 1 week before chemotherapy.
Cardiac function was assessed by conventional echocardiography, tissue Doppler, and strain rate (SR) imaging, which depicts regional myocardial contractility. The researchers also measured plasma levels of reactive oxygen species (ROS; free radicals) and the capacity for antioxidative defenses, the latter by detecting glutathione peroxidase activity. These parameters were assessed at baseline and 7 days after each new 100- mg/m2 dose of epirubicin.
At the 200-mg/m2 epirubicin dose, the SR peak was significantly impaired compared with baseline for both the telmisartan and placebo groups, with no statistical difference between the two groups. As epirubicin cumulative doses increased, however, SR impairment became significantly less pronounced in the telmisartan group compared with the placebo group (P <.001 at both 300 mg/m2 and 400 mg/m2).
At the 200-mg/m2 epirubicin dose, telmisartan limited the production of ROS (463 free oxygen radicals test units [FORT-U] vs 455 FORT-U at baseline; P = not significant), whereas ROS increased in the placebo group compared with baseline (525 FORT-U vs 406 FORT-U, respectively; P <.05) [1 FORT-U corresponds to 0.26 mg/L H2O2]. Glutathione peroxidase activity decreased significantly in both groups at the 200-mg/m2 dose.
The researchers said that these data confirm their earlier findings that epirubicin cardiotoxicity is largely related to inactivation of cardiac antioxidant effects. They concluded that telmisartan can decrease the amount of epirubicininduced free radicals and counteract the early myocardial impairment. They intend to continue the study on a larger cohort of patients.
Another group of researchers reported that granulocyte colonystimulating factor (G-CSF) can protect myocardium and preserve systolic function in patients receiving anthracycline-based chemo therapy. That was the finding of a retrospective cohort study involving patients admitted to the oncology floor of Jackson Memorial Hospital of the University of Miami in Florida between October 2007 and September 2008.
Of 597 patients admitted, 107 had transthoracic echocardiograms prior to the first dose and following the last dose of G-CSF, thereby allowing assessment of baseline and posttreatment left ventricular ejection fractions (LVEFs). Seventy patients received GCSF, and the 37 who did not served as a control group. There were no statistically significant differences in age (mean, 44-48 years), sex, use of beta blockers or angiotensin-converting enzyme inhibitors, proportion receiving cardiotoxic chemotherapy, or number of days between echocardiograms between the two groups.
Lead author Raphael Cires, MD, said that "the patients who received filgrastim have protection in their ejection fraction compared with the patients who did not receive filgrastim." Considering all 107 patients, those who received filgrastim had a posttreatment mean LVEF of 55.8% versus 56.2% at baseline (P = .83). Without filgrastim, the mean LVEF decreased to 55.2% versus 59.7% at baseline (P = .02).
Among the group who received cardiotoxic chemotherapy, specifically doxorubicin, "We found that the difference is even bigger," he said. "The patients who received filgrastim had...almost no variation in the ejection fraction [57.6% vs 59% at baseline, P = .55], and the patients who did not receive filgrastim had a drop of almost 10 points in the ejection fraction [48.8% vs 58.3% at baseline, P = .04]."
Some of the limitations of the study include its small sample size, lack of randomization to treatment with GCSF, and lack of standardization of the G-CSF doses. Cires said a future study will better monitor the amount of GCSF delivered and will use magnetic resonance imaging, the gold standard, to assess LVEF.
He speculated that G-CSF could potentially be used in the future for its cardioprotective effects with anthracycline-based chemotherapy.