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Some patients with incurable tumors and BRCA mutations respond to new 2-drug combination
Date:4/7/2013

WASHINGTONA novel combination of two drugs has shown anti-cancer activity in patients who had incurable solid tumors and carried a germline mutation in their BRCA genes, Dana-Farber Cancer Institute researchers are reporting at the American Association for Cancer Research annual meeting in Washington, April 6-10.

The findings (abstract LB-202) will be released at a press conference on Sunday, April 7, 2 p.m. ET, and later at an oral presentation on Tuesday, April 9, 2 p.m. ET, in Room 153, in the Washington Convention Center.

The two oral drugs, sapacitabine and seliciclib, were given sequentially in a phase 1 clinical trial that is mainly enrolling patients whose tumors lack BRCA function because of an inherited mutation.

"We have seen several responses among these patients, as well as instances of prolonged stable disease lasting more than a year," said Geoffrey Shapiro, MD, PhD, director of Dana-Farber's Early Drug Development Center (EDDC). As a result, he said that a BRCA mutation may be a potential biomarker that identifies patients who are more likely to respond to the drug combination.

Sixteen patients enrolled in the trial carried an inherited BRCA mutation. Four of these patients had partial responses a 30 percent or greater shrinkage of tumor mass including one with pancreatic, two with breast, and one with ovarian cancer. Three patients were continuing to have a partial response at the time of presentation of the data, with the longest lasting more than 78 weeks. Two additional BRCA mutation carriers, with breast and ovarian cancer, experienced stable disease for 21 and 64 weeks, respectively. Of the remaining 22 patients enrolled in the trial, six experienced stable disease for 12 weeks or more.

Sapacitabine is toxic to cancer cells by causing damage to their DNA, which, if not repaired, causes the cells to self-destruct. The BRCA protein is essential for repair of the DNA damage caused by sapacitabine, so patients wit
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Contact: Teresa Herbert
teresa_herbert@dfci.harvard.edu
617-632-4090
Dana-Farber Cancer Institute
Source:Eurekalert

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