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Targeted Therapy Shows Promise Against Deadly Brain Cancer
Date:6/5/2010

Small trial found compound slowed drug-resistant medulloblastoma in children

SATURDAY, June 5 (HealthDay News) -- A preliminary study has found that a targeted treatment for medulloblastoma -- the most common malignant brain cancer in children -- may one day be able to treat drug-resistant forms of the disease.

"Less than 5 percent of patients currently survive medulloblastoma," said Dr. Amar Gajjar, lead author of the study, which was presented Saturday at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago. "Most patients usually die 12 to 18 months after the tumor comes back."

Although this study was designed primarily to assess side effects, if the drug moves through the pharmaceutical pipeline, it would be the first targeted drug aimed at a signaling pathway. Chemotherapy is the main treatment now.

The drug, known as GDC-0449, interrupts the "sonic hedgehog" pathway, which has been implicated in a number of other cancers; it is involved in 20 percent of cases of children with medulloblastoma.

The drug has already been shown to have some effectiveness in adults with medulloblastoma that has recurred, as well as with basal cell carcinoma, a type of skin cancer.

Thirteen children with recurrent or drug-resistant brain tumors took GDC-0449 once a day for 28 days at one of two doses. The median age of the participants was about 12.

Twelve of the participants stayed the course without major side effects. One child was able to continue taking the drug for a full year without the cancer progressing.

"This demonstrates that we have taken a tumor, found a molecular subtype, found a drug which works, showed that it's safe in children and that we can have them benefit by treating these tumors using this molecular targeted therapy," said Gajjar, who is director of neuro-oncology in the department of oncology at St. Jude Children's Research Hospital in Memphis.

The research group will be moving on to a phase 2 trial. A phase 2 trial in adults is already ongoing, Gajjar said.

"Preliminary analysis has shown benefits to these [adult] patients," he noted.

Because this was such an early trial, "we don't yet know what impact this drug is going to have on survival," said Dr. Lynn Schuchter, moderator of a news conference involving the trial and a professor of medicine at the Abramson Cancer Center at the University of Pennsylvania. "We don't have a lot of data on follow-up, but this is really an amazing proof-of-principle idea and this pathway looks to be relevant in many cancers."

Schuchter reported ties to drug maker Pfizer Inc., while Gajjar reported no such ties.

More information

Children's Hospital Boston has more on medulloblastoma.



SOURCES: June 5, 2010, news conference with Lynn Schuchter, M.D., professor, medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, and Amar Gajjar, M.D., director, neuro-oncology division, department of oncology, St. Jude Children's Research Hospital, Memphis, Tenn.; June 5, 2010, American Society of Clinical Oncology annual meeting, Chicago


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