Pfizer, Onyx drug offers hope against brain cancer

LONDON Tue Mar 30, 2010 1:00pm EDT

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LONDON (Reuters) - A drug being developed by Pfizer and Onyx and already in clinical trials against a range of cancers has shown in laboratory tests "a remarkable ability" to halt growth of a deadly type of brain tumor, U.S. scientists said on Tuesday.

Researchers from Georgetown Lombardi Comprehensive Cancer Center and the University of California said the experimental drug, called PD-0332991, may become a new treatment option for glioblastoma, the commonest and deadliest form of brain cancer.

Clinical trials to test the drug in patients with recurrent brain cancer are under development, they said in a study published in the journal Cancer Research.

"We don't know how well this agent will perform in patients with glioblastoma but in the mice we studied we saw very impressive, durable effect," said David James, a professor of neurological surgery at UCSF, who worked on the study.

"What is especially encouraging about this agent is that we found it can easily pass through the blood-brain barrier and access glioblastoma, and that there is already a simple test available for screening glioblastoma patients in advance to see whether or not they should be responsive to this therapy."

Data from a recently-published study by The Cancer Genome Atlas Research Network, suggests about 90 percent of glioblastoma patients would be suitable candidates for the drug, he said.

PD-0332991, which Pfizer is developing under license from Onyx, is being tested in human trials for other cancers such as multiple myeloma and mantle cell lymphoma. It is a pill designed to shut down activity of molecules called cyclin-dependent kinases 4 and 6 (cdk4 and cdk6) that drive cell division.

"In normal cells these kinases are kept under exquisite control by a gene known as p16," said Todd Waldman of Lombardi, who worked on the study with James.

"But in glioblastoma and other cancers, p16 is frequently deleted, and these two kinases are uncontrollably activated, which drives the cell to divide and form cancer."

But the drug does not work if the cancer is missing a protein known as retinoblastoma (Rb). A test for Rb is already being used to screen patients for use of PD-0332991 in the ongoing clinical trials.

In their study James's team implanted three different kinds of human glioblastoma directly into the brains of mice and then treated them with PD-0332991. They found the drug was able to get to the tumors and halt the cancer's growth as long as the mice stayed on the drug.

Because PD-0332991 itself does not kill cancer cells -- just halts their growth -- the researchers then combined the drug with radiation and found the combination worked better than PD-0332991 alone. They also successfully tested the drug in mice in which glioblastoma had come back after treatment with temozolomide, a chemotherapy used in many cancer patients.

(Reporting by Kate Kelland; Editing by Greg Mahlich)

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