Efaproxiral a promising adjunct to radiotherapy for brain metastases
 

Efaproxiral a promising adjunct to radiotherapy for brain metastases

http://www.ascopreview.org/portal/be...go_reuters.gif http://www.ascopreview.org/portal/be...ages/clear.gifhttp://www.ascopreview.org/portal/be...ages/clear.gifPosted: January 30, 2006

http://www.ascopreview.org/portal/be...ages/clear.gif

NEW YORK (Reuters Health) - Phase III study findings suggest that the addition of the radiation sensitizer efaproxiral to whole-brain radiation therapy (WBRT) improves response rates and potentially survival over WBRT alone in patients with brain metastases, particularly those from breast cancer. Efaproxiral is a noncytotoxic synthetic hemoglobin modifier designed to enhance tumor oxygenation and radiation sensitivity by stimulating the release of oxygen from hemoglobin.

"Unlike other agents that have been used to improve the effectiveness of WBRT, efaproxiral does not need to enter cancer cells to increase radiosensitivity because oxygen readily diffuses across the blood-brain barrier to decrease tumor hypoxia," investigators explain in the January 1st Journal of Clinical Oncology. Hypoxic tumors are more resistant to the effects of ionizing radiation.

In the study, 515 patients with brain metastases from solid tumors were randomized to standard WBRT with supplemental oxygen and either efaproxiral (75 or 100 mg/kg) administered intravenously 30 minutes before WBRT (n = 265) or no efaproxiral (n = 250).

The addition of efaproxiral to WBRT and oxygen increased the overall response rate from 38% to 46% (p = 0.10) and median survival time from 4.4 to 5.4 months (p = 0.16).

Larger gains were seen in a subset of patients with non-small-cell lung cancer and breast cancer, for whom the overall response rate improved from 41% to 54% (p = 0.01) and median survival time from 4.4 to 6.0 months (p = 0.07).

"Results from the study are particularly striking considering the limited survival benefit provided by current treatment strategies," study investigator Dr. John H. Suh from the Cleveland Clinic Foundation, Brain Tumor Institute, told Reuters Health.

"Since systemic agents have provided benefit for extracranial disease in breast cancer patients, control of brain metastases will be critical in improving survival for these patients," he added.

The potential survival advantage of efaproxiral plus WBRT observed in this study is particularly compelling, Dr. Suh mentioned, considering the lack of progress made in the field over the past 25 years in extending the survival of a patient population with an otherwise poor prognosis.

Overall, patients tolerated efaproxiral fairly well. The most common adverse event - reversible grade 3 hypoxemia occurring in 11% of the patients in the efaproxiral arm compared with 1% in the control arm - was effectively managed with supplemental oxygen in most patients.

"If additional study shows that efaproxiral significantly improves local control or patient survival, this level of toxicity would be acceptable," Dr. Penny K. Sneed of the University of California San Francisco notes in a related editorial.

Results from this study prompted efaproxiral-maker Allos Therapeutics of Westminster, Colorado to initiate a confirmatory phase III trial in patients with brain metastases originating from breast cancer. The trial is currently enrolling patients at leading cancer centers across North America, Europe and South America and is expected to complete patient enrollment in the second half of 2006.