February 2, 2007

New angiogenesis inhibitor has promise for treating deadly
brain tumor

MGH Cancer Center researchers have found that RECENTIN, a new angiogenesis inhibitor, can significantly reduce the size of brain tumors called glioblastomas and may improve the effectiveness of other therapeutic techniques. The phase 2 clinical trial also finds that this drug can alleviate brain swelling known as edema, a debilitating symptom that currently can be treated only with steroid drugs. Appearing in the January 2007 issue of Cancer Cell, the study is too preliminary to determine whether this new drug may have an impact on overall patient survival.

"Patients with recurrent glioblastomas desperately need new, effective treatment alternatives," says Tracy Batchelor, MD, chief of Neuro-Oncology in the MGH Cancer Center and the study's lead author. "It's looking like these agents may play an increasingly important role in the treatment of those patients and perhaps for newly diagnosed patients as well." (Batchelor is pictured at right.)

Glioblastoma is the most malignant form of brain tumor and has a very poor prognosis. Standard treatments may delay tumor growth, but patients usually survive for little more than a year. Angiogenesis inhibitors suppress the growth of blood vessels supplying a tumor, and some have been shown to improve patient survival when combined with traditional anticancer therapies. That fact supports a theory developed by Rakesh Jain, PhD, director of the Steele Laboratory in the MGH Department of Radiation Oncology, that the agents temporarily "normalize" tumor blood vessels, creating a period during which chemotherapy and radiation treatment can be more effective.

The Cancer Cell paper reports on the first 16 patients to enter the clinical trial of RECENTIN, which has not yet received FDA approval. Participants took a daily oral dose and were followed with regular physical, neurological and MRI imaging exams during the six-month study period. Overall, tumors shrank by at least 25 percent in three-quarters of the study participants and by 50 percent or more in half of the patients. Factors indicating a normalization of the tumors' blood vessels were seen almost immediately in most participants and continued for 28 days to four months, potentially defining how long the period of vascular normalization might last.

"This small group of patients needs to be followed for a longer period of time, but we are cautiously optimistic that this trial and future studies will lead to positive long-term outcomes for some patients," says Jain, the study's senior author. Gregory Sorensen, MD, co-director of the Athinoula A. Martinos Center for Biomedical Imaging, is the co-lead author of the report.