Article on Cardiotoxicity

Joe · 06-15-2007, 09:09 AM

Normally I would just place a link but I feel this article is Important !!

Newer Breast Cancer Drug May Protect Heart, Study Suggests
Science Daily — By uncovering how one breast cancer drug protects the heart and another does not, "It is important to be clear that we are reporting findings from pre-clinical experiments, so while they suggest a difference between these two agents, it would be over-interpreting the study to conclude that women taking trastuzumab should consider any treatment change," Spector said. "However, it may be important to conduct well-controlled clinical trials to answer this question."
In addition to its association with breast cancer, HER2 is also essential for the early development and later sustenance of heart muscle cells. It appears that trastuzumab's mechanism for blocking HER2 is different.
"We found that lapatinib activates a critical pathway that protects heart cells from 'committing suicide' as a result of stress," Spector continued. "Heart muscle cells require a tremendous amount of energy to function properly and are therefore extremely sensitive to energy deprivation as a consequence of reduced oxygen or nutrient supply. In addition, heart muscle cells appear to be sensitive to the death promoting effects of inflammation.
"Our experiments in isolated human heart muscle cells indicate that lapatinib activates a pathway that protects cardiac muscle cells from the death-promoting effects of mediators of inflammation, which are activated in cancer patients, particularly those who have received chemotherapies that damage heart tissue," Spector said. "In contrast, trastuzumab does not activate this protective pathway."
With clinical trials currently investigating the combination of lapatinib with trastuzumab, there is a possibility that the effects of lapatinib in cardiac muscle cells might protect the heart against potential toxicity associated with trastuzumab, Spector added.
More broadly, Spector said that these findings of how lapatinib bestows cardiovascular protection during times of stress -- whether from chemotherapy or heart muscle cells deprived of oxygen during a heart attack -- could be used in other situations.
"Using this system, we could theoretically screen drugs that are in the development phase to see what their effects may be on heart muscle cells," Spector said. "We may be able to select the drug candidates that have the fewest cardiovascular side effects and theoretically would be safer for patients. This way, we could find out about some of these potential problems long before the drugs even make it to market."
Additionally, Spector said there is the potential for the development of similar drugs that can be used as protective agents in situations where the heart is stressed for periods of time, such as during heart attacks, coronary artery bypass surgery or angioplasty. Such a drug could even be used to preserve cardiac function in hearts being harvested for transplant, he said.
The study was supported in part by the <ST1

Duke<?xml:namespace prefix = st1 ns = "urn:schemas-microsoft-com[IMG]http://her2support.org/vbulletin/ /><st1:PlaceName><st1:PlaceType>University</st1:PlaceType><st1:PlaceName>Medical</st1:PlaceName><st1:PlaceType>Center</st1:PlaceType> researchers believe they may have opened up a new way to screen drugs for possible heart-related side effects and to develop new drugs.

The Duke researches compared the actions of two breast cancer drugs in experiments involving human cells and rats. The drugs in question were the older drug trastuzumab, whose trade name is Herceptin, and the newer drug lapatinib, whose trade name is Tykerb.
The main side effect of trastuzumab is that it can damage heart muscle cells. Heart abnormalities have been detected in 2 to 7 percent of women taking the drug, and about one in ten women cannot take the drug because preexisting heart problems put them at greater risk for heart damage. To date, there appear to be fewer cardiac effects associated with lapatinib therapy.
Both drugs are prescribed to women whose cancerous breast cells have HER2 genes that are overactive. Approximately one in four women with breast cancer have this overactive gene, which is associated with increased cancer recurrence and worse outcomes. Lapatinib was approved earlier in March for use in women who have not responded to trastuzumab therapy.
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lace. The results of the study appear early online in the journal Proceedings of the National Academy of Science.
Other members of the team were Wenle Xia, Duke; Yosef Yarden and Rony Seger, Weizman Institute, Rehovot, Israel; Bradley Smith, Cell Signaling Technologies, Beverly, Mass.; and Ljuba Lyass, Patricia Trusk, Karen Pry, Jason Hill and Sarah Bacus, Targeted Molecular Diagnostics, Westmont, Ill.
Note: This story has been adapted
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Donna · 06-15-2007, 11:15 AM

Hello Joe,

Thanks for this information. My lvef function has dropped significantly twice now and maybe this is something to talk to my oncologist about. I am concerned since Dr. Slamon said in a talk I heard about that heart issues can come up long after herceptin treatment has ended. I would have to assume that if it effects your heart during treatment, I might be a likely candidate for further problems later.

Food for thought, thanks!

Donna

Lolly · 06-15-2007, 01:15 PM

Very interesting to me, especially in regards to my post yesterday about the results of my heart echo:

Heart doing GREAT on Tykerb

Just wanted to post my Echo results after a month on Tykerb and two months off Herceptin: my LVEF is 65%!
Last year my Muga came in at 49%, the lowest since starting Herceptin in 2001. The number has been slowly but surely declining over the years, so when my onc ordered the Echo after our last visit when I complained of tiredness(red counts are decent), I was a bit worried that Tykerb was affecting my heart function and dropping it even lower...NOT SO! My heart has bounced back and I'm so relieved!

Just wanted you all who may be worried about Tykerb affecting the LVEF, it ain't necessarily so!

<3 Lolly
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