New drug may aid brain cancer treatment

University scientists say they’ve seen some success with a new approach to treating the more than 170,000 cancer patients in the U.S. whose cancer spreads from another part of their body to their brain each year .

A new drug may increase tumor response rates and reduce progression of the disease, according to a study published in this week’s Journal of Clinical Oncology.

The multi-center phase Ib/II clinical trial of the investigational agent, motexafin gadolinium administered in combination with standard whole brain radiation therapy, showed the treatment increased local tumor control, as evidenced by a high tumor response rate (i.e., significant tumor shrinkage) and low rate of death due to tumor progression in the brain. A trial seeks to determine both proper dosage and effectiveness of the drug.

“We are particularly pleased to see the high tumor response rate, which is nearly double what we have observed in the literature with radiation alone,” says Minesh Mehta, associate professor and interim chair, Department of Human Oncology, Comprehensive Cancer Center, one of the study’s lead investigators. “Based on these encouraging results, we conducted a large multi-center international Phase III study designed to measure survival and time to neurologic progression in a similar patient population. Enrollment in this 428-patient trial has been completed, and we expect to report results by the end of this year.”

Motexafin gadolinium is the first of a new class of drugs called texaphyrins. It selectively accumulates in cancer cells and disrupts cellular metabolism by a unique mechanism of action. By interfering with the flow of energy in cancer cells, motexafin gadolinium makes the tumor more responsive to the effects of radiation and chemotherapy without increasing damage to normal tissue.

Sixty-one patients with brain metastases were enrolled in the combined trial. For 10 days, daily intravenous injections of motexafin gadolinium were administered, followed by whole brain radiation treatment each day. The treatment was well tolerated. The most common side effects observed were discoloration of the skin, urine and eyes due to the dark-green color of the drug. The discoloration developed gradually after repeated drug dosing, and cleared three to four days after the last dose.

“This is the first treatment of its kind that appears to enhance the beneficial effects of radiation therapy in a clinical setting,” says Patrice Carde, Chef de Service, Department of Medicine, Institut Gustave Roussy, Villejuif, France, lead author of the study.

About 170,000 patients are diagnosed with brain metastases each year in the United States. This number is increasing as cancer patients live longer due to new treatment advances made in the last several years. However, there are few treatment options for patients whose cancer has advanced and spread to the brain.

Metastases in the brain are one of the most devastating consequences of cancer, affecting up to 40 percent of all cancer patients. The majority of brain metastases originate in breast and lung cancers. Brain metastases occur when cancer cells from the primary site migrate (often through the blood stream) and travel to the brain, where they remain and grow. Patients with brain metastases may suffer devastating complications from uncontrolled progression of tumor growth in the brain; these complications include headaches, seizures, paralysis, blindness, neurocognitive deterioration and death. The goal of whole brain radiation therapy is to reverse or prevent neurological deterioration and prevent death due to tumor progression in the brain.

The Comprehensive Cancer Center is one of 37 multidisciplinary comprehensive centers funded by the National Cancer Institute. The UW–Madison center offers standard and innovative cancer treatment to patients. The center’s research focuses on common cancers such as breast, lung and prostate and also emphasizes disease prevention. The research is heavily dependent on federal grants and gifts from individual donors.