The drug XcytrinŽ, based on a molecule developed by chemists at The University of Texas at Austin, shows significant promise in prolonging cognitive function in patients with non-small cell lung cancer that has metastasized to the brain.
This result, presented at the annual meeting of the American Society of Clinical Oncology on June 5, supports Pharmacylics, Inc.'s recent decision to file a New Drug Application with the U.S. Food and Drug Administration.
In a Phase 3 trial, Xcytrin was delivered in conjunction with whole brain radiation treatment to patients with non-small cell lung cancer that had spread to the brain. Xcytrin significantly prolonged the time to neurologic progression, which is described as a change in mental status, vision and muscle strength associated with the progression of brain cancers.
"In conjunction with radiation, Xcytrin enhances cancer cell death," said Dr. Jonathan Sessler, professor of chemistry and biochemistry and co-founder of Pharmacyclics (Sunnyvale, Calif., PCYC). "Radiation puts stress on the cells and the drug puts further stress on the cells. Add them together and the cells start to die."
More than 500 patients from North America, France and Australia participated in this Pharmacyclics trial combining Xcytrin injection with whole brain radiation. In North America, patients receiving the treatment experienced neurologic progression 16 months later than patients not receiving the treatment.
Xcytrin (motexafin gadolinium) is based on texaphyrin molecules developed in Sessler's lab. Texaphyrins are large, "Texas-sized" versions of porphyrins, which are highly pigmented molecules responsible for the color of red blood cells. Texaphyrins localize to cancer cells and disrupt cellular metabolism and energy production, weakening or destroying the cells. The molecules are relatively non-toxic to normal cells.
Sessler's texaphyrins were designed to hold heavy metals like gadolinium, commonly used to produce magnetic resonance imaging (MRI) agents. As a consequence, Xcytrin allows tumors to be visualized through MRI. The ability to both detect and treat brain and other cancers using the same agent could prove advantageous in a clinical setting, which Pharmacyclics and its collaborators are studying in the context of ongoing early stage clinical trials. Other trials are now underway to test the potential of Xcytrin to act as a stand-alone chemotherapeutic agent or in combination with other known cancer drugs.
Lee Clippard
lclippardmail.utexas.edu
University of Texas at Austin
utexas.edu/