Drug shows promise in fighting brain tumors

Early results from an ongoing cancer drug study shows that a new agent, Xcytrin (motexafin gadolinium), demonstrates a high response rate and is well-tolerated in patients with brain metastases – brain tumors that originate from cancer in another part of the body.

“We are excited by the possibility of prolonged survival and enhanced quality of life suggested by these initial findings, particularly given the lack of effective treatments for brain metastases.” Minesh Mehta Principal investigator

The study results were presented today (Monday, Nov. 1) in San Antonio at the 1999 Annual Meeting of the American Society for Therapeutic Radiology and Oncology.

“While these results are preliminary, we saw a significant amount of tumor response and a low rate of tumor progression in the brain with Xcytrin followed by whole brain radiation treatment,” said the study’s principal investigator, Minesh Mehta of the UW Comprehensive Cancer Center and associate professor and interim chair of the Department of Human Oncology at the UW Medical School. “We are excited by the possibility of prolonged survival and enhanced quality of life suggested by these initial findings, particularly given the lack of effective treatments for brain metastases.”

Xcytrin selectively accumulates in brain metastases and enhances the cancer-killing effects of radiation.

Brain metastases are the most common form of brain tumors, considerably outnumbering primary brain tumors by approximately 150,000 new cases each year in the United States. Brain metastases are becoming increasingly common, and their treatment represents a critical unmet medical need, Mehta said.

Brain metastases occur when cancer cells spread to the brain and grow, causing major neurologic complications and, in many cases, death.

Patients with brain metastases usually suffer serious deterioration of neurocognitive function such as loss of short-term memory, compromised verbal skills and fine motor coordination and reduction in cognitive performance.

The goal of whole brain radiation therapy is to reverse or prevent neurological deterioration and to prevent death due to tumor progression in the brain.

In the lead-in phase of the ongoing open-label, randomized Phase III clinical trial, 25 patients with brain metastases (including 7 patients at the Comprehensive Cancer Center) were treated with Xcytrin followed by standard whole brain radiation therapy for 10 days.

MRI results were available for 19 patients. Significant tumor shrinkage (response) was seen in 68 percent of the patients.

Tumor response was measured by serial MRI scans and defined by at least a 50-percent reduction in tumor volume.

The study showed tumor progression in 16 percent of the evaluable patients.

All 25 patients were evaluable for neurocognitive (brain) function and survival. Nineteen patients maintained or improved their brain function; six patients experienced deterioration of brain function. One patient died due to brain tumor progression.

Treatment with Xcytrin was well tolerated. Side effects observed included nausea in three patients, fatigue and weakness in two patients and reversible abnormalities of liver enzymes in two patients.

Patients enrolled in this study had advanced disease. Nineteen were ineligible for radiosurgery due to the advanced status of the tumors.

The Phase III study, currently being conducted at 40 medical centers in the United States, Canada and Europe (including the UW Comprehensive Cancer Center) will compare the treatment of brain metastases with whole brain radiation alone to whole brain radiation therapy plus Xcytrin. A total of 425 patients will be enrolled in the study, including this first group of 25 patients whose results were announced today (Monday, Nov. 1).