Source: DGNews  |  Posted 2 years ago

By Jill Stein

SAN ANTONIO, Tex -- December 11, 2009 -- Researchers are reporting favourable cardiac safety data for casopitant when used with anthracyclines in chemotherapy-naïve patients with a malignant solid tumour.

The results were presented on December 10 at the 32nd Annual San Antonio Breast Cancer Symposium (SABCS) by Michael S. Ewer, MD, University of Texas M. D. Anderson Cancer Center, Houston, Texas.

“Cardiac troponin, a biomarker of cardiac damage, is known to be elevated following treatment with anthracyclines, which are commonly included in the chemotherapeutic regimen for patients with breast cancer,” said Dr. Ewer. “Assessment of the cardiac effects of supportive interventions such as casopitant is critical to avoid increased risk of cardiovascular damage.”

The phase 3 study included chemotherapy-naïve patients receiving anthracyclines as part of a moderately emetogenic chemotherapy study regimen.

Patients were randomised to receive ondansetron and dexamethasone plus 1 of the following casopitant regimens: single-dose oral casopitant 150 mg/day (ORAL1); 3-day intravenous (IV)/oral casopitant -- 90 mg IV/50 mg oral/50 mg oral (IV/ORAL); 3-day oral casopitant 150/50/50 mg (ORAL3); or placebo.

Of the study population, 96% of patients were being treated for breast cancer. Overall, 611 patients were evaluated.

Adverse events were similar in all treatment groups.

Cardiovascular adverse events occurred in 3% of patients in each of the placebo, ORAL1, and ORAL/IV groups, and in 2% of the ORAL3 group.

Normal cardiac troponin levels (<0.04 ng/mL) were observed in most patients. No patient had any sample with a cardiac troponin value >=0.50 ng/mL.

Three patients had cardiac troponin levels above the prospectively defined threshold of 0.12 ng/mL for entry into the cardiovascular follow-up phase, and 2 of these patients had values returning toward normal at 3 months.

A total of 59 patients had median cardiac troponin values of 0.04-0.12 ng/mL. Of the remaining patients with cardiac troponin levels below the limit of quantification, the median baseline levels across groups were similar (ORAL1 and IV/ORAL 0.008 ng/mL; ORAL3 0.01 ng/mL; placebo 0.009 ng/mL).

After 4 cycles of anthracycline, median cardiac troponin increased to 0.02 ng/mL in all groups, with no difference observed between the casopitant and placebo cohorts.

Overall, reported cardiac serious adverse events and electrocardiogram and left ventricular ejection fraction data showed no evidence of an increased risk of cardiac damage in the casopitant groups.

“Subclinical cardiac damage may result in increases in cardiac biomarkers that occur in ranges below those commonly used to detect infarction,” Dr. Ewer concluded. “Appreciation of these changes may be valuable to detect or exclude subclinical toxicity of potentially cardiotoxic agents, especially when they are used in combination.”

Funding for this study was provided by GlaxoSmithKline.

[Presentation Title: Cardiac Safety Data for Casopitant, a Neurokinin-1 Receptor Antagonist, Given With Anthracycline. Abstract 1118]