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Breaking a Barrier in Brain Cancer

June 17, 2011

 

Brain cancer is one of the most deadly cancers, in part because chemotherapy drugs injected into the bloodstream cannot get past the blood-brain barrier and into the brain.

But that may start to change if the results of a small clinical trial involving a new way to deliver chemotherapy are any indication.

The trial shows that “convection enhanced delivery” – which allows chemotherapy drugs to be pumped straight into the tumor, bypassing the barrier – has the potential to shrink brain tumors and increase survival, says the trial’s principal investigator, Jeffrey Bruce, MD, Edgar M. Housepian Professor of Neurological Surgery and director of the Bartoli Brain Tumor Research Laboratory.

WHAT’S WRONG WITH BRAIN CANCER TREATMENT NOW?

Most patients with brain tumors undergo surgery, which removes the bulk of the original tumor. But without effective chemotherapy, leftover cells spread and reestablish the cancer. Most patients die a few months after relapse.

“It’s not that the drugs don’t work,” Bruce says. Several drugs on the market show significant activity against brain cancer in lab settings. “It’s that you can’t get enough of the drug into the tumor where you need it.”

CAN A PUMP DO BETTER?

By delivering a higher concentration of chemotherapy directly to the brain tumor and surrounding tissue, a pump and catheter strategy could improve survival. But so far, convection enhanced delivery has not been successful, possibly because the drug chosen for infusion was too toxic to the brain.

WHY IS THE COLUMBIA TRIAL DIFFERENT?

For the Columbia trial, Bruce chose a drug not normally used against brain cancer after lab tests revealed that the drug, called Topotecan, kills glioma cells but leaves normal brain cells alone.

Bruce and his colleagues recruited 16 patients with malignant glioma into the trial. Most patients had undergone surgery to remove the initial tumor, but the cancer had since returned. A tube – connected to an external pump – was surgically implanted so that Topotecan slowly dripped into the tumor over a four-day period. Doses of Topotecan were escalated during the trial until the investigators found the maximum tolerated dose.

WHAT DO THE RESULTS SHOW?

Even at drug doses lower than the maximum tolerated dose, many tumors shrank. Overall, 69 percent of patients responded to the drug, and median survival was 60 weeks.

 MRI scans show tumor regression in a patient with one of the best responses to the new treatment.

“Given that these patients hadn’t had success with other treatments, nearly any response rate is significant and encouraging,” Bruce says. Median survival, he adds, was higher than that of control groups in other clinical trials with brain cancer patients and, more importantly, was safe.

The drug did not affect neurocognitive function, and the researchers found no toxic effects of the drug outside the brain. The findings appear online in the journal Neurosurgery.

WHAT’S NEXT?

A larger randomized clinical trial needs to be conducted to determine the true effectiveness of the system. “We’re probably at the limit now of what we can do surgically for these patients, Bruce says. “I’m optimistic that if we can deliver as much chemotherapy as possible without worrying about side effects, we can do better.”

--Susan Conova

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