New Cancer Drug Tied to Heart Problems

THURSDAY, Dec. 13 (HealthDay News) -- The new and powerful cancer drugsunitinib (Sutent), which fights stomach tumors, can also create heartproblems for some patients, a new study finds.
All patients taking sunitinib, but especially those who have risks forheart disease, need careful monitoring and treatment for high bloodpressure and other signs of heart problems, researchers say.
"All drugs have risks and benefits," noted lead researcher Dr. Ming HuiChen, an assistant professor of medicine at Harvard Medical School and acardiologist at Children's Hospital Boston. "This drug is lifesaving forpeople with metastatic, gastrointestinal stromal tumors," she added.
But it is important for both doctors and patients to be aware thatsunitinib can have cardiac effects, Chen noted.
"The people at greatest risk are the people who have a history ofcoronary artery disease," Chen said. "Aggressive control of bloodpressure in these patients is very important."
In a statement released Thursday, sunitinib's maker, Pfizer Inc.,agreed that these heart risks do exist. However, they added that thecardiovascular events "were medically manageable in most patients andunderscore the importance of having a collaborative team of healthcareprofessionals working together to appropriately manage patients, who havelimited available options" in treating their cancer.
The new, collaborative study was supported by Children's HospitalBoston; the Dana-Farber Cancer Institute; Thomas Jefferson University; theU.S. National Heart, Lung, and Blood Institute; the Finnish HeartFoundation; and the American Heart Association.
Sunitinib is one of a family of new and powerful anti-cancer drugscalled tyrosine-kinase inhibitors, which target key molecular pathwaysthought to encourage tumor growth. Other drugs in this family includeimatinib, better known as Gleevec, and dasatinib (Sprycel).
In the study, which is published in the Dec. 15 issue of TheLancet, Chen's team looked at 75 patients with metastatic,gastrointestinal stromal tumors that had not responded to standard therapywith Gleevec. The patients had taken part in a phase I/II trial studyingthe efficacy of sunitinib.
The researchers looked back at the medical records of these patients,noting those who died from heart disease or had suffered heart attacks orcongestive heart failure. They also looked at the effect of sunitinib onthe heart's ability to pump blood and on blood pressure.
Chen's group found that eight patients given repeated cycles ofsunitinib had cardiovascular events. Two had heart attacks, and six hadheart failure. Of 36 patients given the approved dose of sunitinib, 10 hada 10 percent or more reduction in the ability of their heart to pumpblood, and seven had a 15 percent or more reduction in heart function.
In addition, sunitinib was associated with increases in blood pressure,with a total of 35 (47 percent) of the patients developing hypertension.However, these effects were not permanent: When sunitinib treatment wasstopped and patients began therapy to ease heart problems, levels of heartfailure and heart functioning improved, the researchers found.
"Most of the patients who had heart problems were able to resume takingsunitinib with either a modification in their dose or initiation of heartfailure medication," Chen said.
In addition, in experiments with mice and rat heart cells, Chen's teamfound that sunitinib triggered heart cells damage and death.
However, in their statement, Pfizer noted that, "Lower incidences ofcardiovascular effects have been observed in subsequent randomized Phase 3prospective Sutent studies in both renal cell carcinoma andgastrointestinal stromal tumor[s]." That includes a lower incidence ofevents such as congestive heart failure, impaired heart function, and highblood pressure that were noted in Chen's retrospective analysis, thecompany said.
Chen stressed that patients taking sunitinib who develop shortness ofbreath and fatigue and swelling of the arms or legs should be checked forheart problems. "These symptoms can be ascribed to cancer, but since thisdrug may have a cardiovascular effect, these may be signs of heartproblems," she said.
One expert said the findings must be approached with caution.
"The findings are intriguing, but one has to be careful aboutgeneralizing them," said Dr. James Brugarolas, an assistant professor inthe division of oncology at Simmons Comprehensive Cancer Center at theUniversity of Texas Southwestern Medical Center at Dallas. "It's a smallgroup of patients, many of whom were taking other drugs that can havecardiac effects," he said.
However, patients who have coronary artery disease who are going to begiven sunitinib should be very carefully monitored for the development ofheart failure, Brugarolas said. "There should be a proactive attitude onthe part of the physician to manage hypertension," he added.
Brugarolas also noted that sunitinib has been shown to slow theprogression of gastrointestinal stromal tumors but not to extend patients'overall survival. "These side effects may be affecting survival," he said."If survival is compromised by adverse effects of the drug, then it maynot be beneficial to patients."
More information
For more on sunitinib, visit the U.S. National Library of Medicine.