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Lapatinib and pazopanib combo not found to improve outcomes forpatients with inflammatory breast ca by e55he swrzsnb





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Lapatinib and pazopanib combo not found to improve outcomes forpatients with inflammatory breast ca by
Article Posted: 12/14/2013
Article Views: 94
Articles Written: 2033
Word Count: 604
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Lapatinib and pazopanib combo not found to improve outcomes forpatients with inflammatory breast ca


 
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Inflammatory breast cancer is a very aggressive type of cancer associated with early metastasis and poor survival rates, and theprognosis is even worse for patients with tumors expressing theErbB2 receptor. The ErbB2-inhibiting drug lapatinib can slow thespread of cancer cells in individuals with advanced breast cancerwho have already tried other chemotherapy medications. Treatingthese patients with a combination of drugs has the potential toimprove outcomes compared to treatment with lapatinib alone, but ithas not been clear whether the additional benefits outweigh therisks. Now, researchers from Fox Chase Cancer Center and theirinternational collaborators have presented information at the 2012Annual Meeting of the American Society of Clinical Oncology thatwill give clinicians the information needed to make that call. Massimo Cristofanilli, M.D., F.A.C.P., professor of medicine at FoxChase's department of medical oncology and lead investigator of thestudy, and colleagues, conducted a randomized, prospective phase IIclinical study to test the effectiveness of combination therapyconsisting of lapatinib and pazopanib - a drug already approved totreat advanced kidney cancer that works by inhibiting the growth of new blood vessels, whichcan also contribute to breast cancer progression.

They found thatcombination therapy produces greater toxicity without significantclinical benefits in patients with inflammatory breast cancer, whencompared with lapatinib treatment alone. The multicenter trial consisted of patients with relapsedinflammatory breast cancer who had tumors expressing the ErbB2receptor. In a group of 76 patients, individuals who receivedlapatinib and pazopanib had an overall response rate of 45 percentand median progression-free survival of about 14 weeks, comparedwith 29 percent and about 16 weeks, respectively, in patients whowere treated with lapatinib alone. "But the differences in efficacywere not statistically significant," Cristofanilli says. In addition, side effects such as diarrhea , vomiting and liver dysfunction occurred in patients undergoingcombination therapy, but not in individuals who only tooklapatinib.

As a result, 21 percent of the patients undergoingcombination therapy required dose reductions and 55 percentrequired dose interruptions, compared with only 3 percent and 11percent, respectively, of patients who only took lapatinib. Because of the side effects experienced by the first group ofpatients, Cristofanilli and his team used lower doses of lapatiniband pazopanib in a second group of 87 patients. Combination therapyresulted in an overall response rate of 58 percent and medianprogression-free survival of 16 weeks, compared with 47 percent and16 weeks for lapatinib alone, and 31 percent and about 11 weeks forpazopanib alone. "Once again, the outcomes in patients who receivedcombination therapy were not significantly better than those inpatients who took lapatinib alone," Cristofanilli says.

Moreover, signs of liver dysfunction, diarrhea and fatigue were more common in patients who received combination therapy thanin those who were treated with a single drug, and these sideeffects resulted in more frequent dose reductions and interruptionsin patients undergoing combination therapy. "The results demonstrate that combination therapy consisting oflapatinib and pazopanib increases side effects, but does notsignificantly improve clinical outcomes, when compared withtreatment with lapatinib as a single agent," Cristofanilli says."Based on these findings, I don't recommend that this type ofcombination therapy be used to treat patients with inflammatorybreast cancer, but we were able to confirm that lapatinib is aneffective treatment for women with this disease." To follow up on this research, Cristofanilli will continue to studyhow the growth of new blood vessels contributes to inflammatorybreast cancer. "This particular type of disease requires moreattention," he says. "We need to continue to investigate thebiology of this disease and try to design better therapies forthese patients." Additional References Citations.

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