An experimental surgery for brain cancer in which patients take a drug that causes tumor tissue to appear fluorescent during an operation seemed to be superior to conventional surgery in a randomized clinical trial.

The multicenter phase III trial, in Germany, involved 270 patients treated for malignant glioma, the most common brain cancer.

Patients who took the drug were more likely to have their tumors removed completely and to be free of disease 6 months after the procedure than patients who had conventional microsurgery with white light.

The drug is a natural compound called 5-aminolevulinic acid. When taken about 3 hours before surgery, it induces the synthesis of fluorescent molecules in cancerous tissue, which can be seen by surgeons through special operating microscopes.

Some previous studies have suggested that treatments for malignant glioma are most effective when all or most of the cancer has been surgically removed.

The trial tested the idea that fluorescence can help guide surgeons during the difficult task of trying to identify and remove the abnormal areas without harming the healthy brain. The borders between these tissues are often unclear.

The researchers say that surgery with 5-aminolevulinic acid is "easy to do and does not interrupt the operation."

"We are using the approach in all our patients undergoing surgery for malignant gliomas in a compassionate use program," says Dr. Walter Stummer of the Heinrich-Heine University in Düsseldorf, who led the trial.

The trial was stopped early after an interim analysis of the results clearly favored the experimental group. It is not yet known, however, whether patients who have the experimental surgery live longer than other patients.

According to findings published in the May Lancet Oncology, tumors were completely removed in 65 percent of the experimental group and 36 percent of conventional group. Side effects after surgery were similar between the two groups a week after surgery.

The experimental strategy was associated with a clinical benefit. After 6 months, 41 percent of the experimental group had not relapsed, compared with 21 percent in the conventional group.

An editorial accompanying the results observes that many tools have been developed to improve the outcomes of surgeries for this disease, but few have been tested in prospective clinical trials.

The trial "is a step forward in the study of surgery for malignant glioma," write Drs. Fred Barker of Massachusetts General Hospital and Susan Chang of the University of California, San Francisco.

They caution, however, that the study did not show a significant overall survival benefit. "The best estimate of the overall survival benefit was modest - about 1.7 months," says Dr. Barker.

For reasons that are not yet clear, the results show a strong correlation between the complete removal of tumors and a patient's age and performance on tests. Patients older than age 55 seemed to benefit more than younger patients.

"I found it interesting that patients in the experimental group had fewer repeat surgeries but tended to survive longer," says Dr. Stummer. This demonstrates how much "patients profit from simply having better surgery at the beginning of therapy."

For patients with malignant glioma, he continues, the goal should be the complete surgical removal of tumors. "Surgery with 5-aminolevulinic acid is a modern, simple, cost-effective, and safe way of achieving this goal," he says.

By Edward R. Winstead