番茄社区

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ORLANDO -- Cardiotoxicity from breast cancer drugs was about half as likely with prophylactic use of heart drugs in higher-risk patients, one trial showed, while a second suggested an early trend for less cardiac damage.

In a randomized trial of 468 HER2-positive breast cancer patients getting trastuzumab (Herceptin) with prior exposure to anthracycline chemotherapy -- both associated with cardiac damage -- the risk of losing at least 10% of left ventricular ejection fraction (LVEF) or at least 5% if to a level below 50% was:

• 51% lowered by the beta-blocker carvedilol (Coreg) versus placebo (P=0.009)
• 47% reduced by the ACE inhibitor lisinopril versus placebo (P=0.015)

Nonsignificant trends in the same direction were seen for the entire cohort when considering patients with exposure to trastuzumab but potentially lower cardiotoxicity risk from receiving chemotherapy regimens using non-anthracycline drugs, Maya Guglin, MD, PhD, of the University of Kentucky in Lexington, reported here at the American College of Cardiology (ACC) annual meeting.

In the 200-patient CECCY trial presented at the same late-breaking clinical trial session, giving carvedilol for 20 weeks during anthracycline-based chemotherapy regimen did not reduce the proportion of women with at least a 10% drop in LVEF (15% versus 14% placebo).

However, there were significant reductions in troponin I and in diastolic dysfunction with carvedilol as well as a trend for less increase in LV diastolic diameter, Monica Avila, MD, of the Heart Institute of the Universidade de São Paulo, Brazil, reported, with simultaneous publication in the Journal of the American College of Cardiology.

Given the short 6-month follow-up in the trial and the lower than expected event rates, it may be that the impact of those lower markers of damage will show up later in the planned 2-year follow-up, Avila suggested.

ACC press conference discussant Bonnie Ky, MD, of the University of Pennsylvania in Philadelphia, said she agreed that the findings supported carvedilol. "I think it's critically important to look at the longer term changes in ejection fraction. We know that changes in EF usually occur 1 to 2 years after the initiation of chemotherapy, and I expect that we will see a benefit of carvedilol there."

Putting all the data together on cardioprotective trials for cancer patients, "these two medications do have cardioprotective benefit," she stated. "For me in my practice, I think high- risk patients should likely be prophylactically treated with these medications. Some oncologists are pulling away from anthracyclines and trastuzumab because of this concern of cardiotoxicity but perhaps we can envision a paradigm where we perform risk-benefit analysis ... we mitigate that cardiotoxic risk with these medications and then overall over the long term hopefully have improved oncologic outcomes."

Guglin said that the oncologists she's talked to said they would increase their use of anthracyclines if they could reduce the cardiovascular risks.

But as even one extra drug is a hard sell to the oncology community, combination is likely out, she noted. "Forget about two extra drugs," she said.