Drug targeting BRCA gene mutations shows promise in prostate cancer

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Patients with inherited forms of advanced prostate, breast, and ovarian cancers caused by mutations in the BRCA1 and BRCA2 genes experienced tumor shrinkage without major side effects when treated with the investigational drug olaparib (AZD-2281), a recently published phase I study showed.

Patients with inherited forms of advanced prostate, breast, and ovarian cancers caused by mutations in the BRCA1 and BRCA2 genes experienced tumor shrinkage without major side effects when treated with the investigational drug olaparib (AZD-2281), a recently published phase I study showed.

Despite having previously received many standard therapies, more than half of the patients in the study saw their tumors shrink or stabilize. One of the first patients to be given the treatment is still in remission after 2 years, according to study authors from the Institute of Cancer Research and the Royal Marsden Hospital, Sutton, United Kingdom. Their findings were published in the New England Journal of Medicine (2009; 361:123-34).

Olaparib, an inhibitor of poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP), targets cancer cells but leaves healthy cells relatively unscathed, researchers say. Importantly, patients experienced very few side effects and some reported the treatment was easier to tolerate than chemotherapy.

Johann de Bono, MD, PhD, a principal investigator, said the positive results confirmed that olaparib should be taken into larger patient trials.

"This drug showed very impressive results in shrinking patients’ tumors," Dr. de Bono said. "It’s giving patients who have already tried many conventional treatments long periods of remission, free from the symptoms of cancer or major side effects."

Olaparib is the first successful example of a new type of personalized medicine using "synthetic lethality," in which the treatment works in combination with a patient’s own specific molecular defect, according to Dr. de Bono and colleagues.

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