Originally published as JCO Early Release 10.1200/JCO.2004.00.1768 on November 28 2005

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Phase III Study of Efaproxiral As an Adjunct to Whole-Brain Radiation Therapy for Brain Metastases

From the Cleveland Clinic, Cleveland, OH; University of Arizona Health Sciences Center, Tucson; Barrow Neurological Institute, Arizona Oncology Services, Phoenix, AZ; US Oncology Research Inc, Dallas; The University of Texas M.D. Anderson Cancer Center, Houston, TX; Allos Therapeutics Inc, Westminster, CO; Wake Forest University School of Medicine, Winston-Salem, NC; Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke; Hôtel-Dieu de Québec du Centre Hospitalier de Québec CHUQ, Québec City; and Hospital Maisonneuve-Rosemont, Montréal, Québec, Canada

Address reprint requests to John H. Suh, MD, Cleveland Clinic Foundation, Brain Tumor Institute, Department of Radiation Oncology, T28, 9500 Euclid Ave, Cleveland, OH 44195; e-mail: suhj{at}ccf.org

PURPOSE: To determine whether efaproxiral, an allosteric modifier of hemoglobin, improves survival in patients with brain metastases when used as an adjunct to whole-brain radiation therapy (WBRT).

PATIENTS AND METHODS: Patients with brain metastases from solid tumors and a Karnofsky performance score of 70 were randomly assigned to receive WBRT with supplemental oxygen and either efaproxiral at 75 or 100 mg/kg (efaproxiral arm) or no efaproxiral (control arm). The primary end point was survival.

RESULTS: The study consisted of 515 eligible patients (efaproxiral arm, n = 265; control arm, n = 250). The median survival time (MST) was 5.4 months for the efaproxiral arm versus 4.4 months for the control arm (hazard ratio [HR] = 0.87; P = .16). For the subgroup of patients with non–small-cell lung cancer (NSCLC) or breast cancer, the MST was 6.0 and 4.4 months, respectively (HR = 0.82; P = .07). Cox multiple regression analysis demonstrated a significant reduction in the risk of death for the efaproxiral arm in both primary populations. Further analysis indicated that the benefit may be restricted to the subgroup of patients with breast cancer. Response rates (radiographic complete response plus partial response) improved by 7% (P = .10) and 13% (P = .01) for all patients and for NSCLC and breast cancer patients in the efaproxiral arm, respectively. The most common severe adverse event in patients treated with efaproxiral was hypoxemia, which was reversible and effectively managed with supplemental oxygen in most patients.

CONCLUSION: The addition of efaproxiral, a noncytotoxic radiation sensitizer, to WBRT may improve response rates and survival in patients with brain metastases, particularly metastases from breast cancer. A confirmatory trial for breast cancer patients has been initiated.

Supported by Allos Therapeutics Inc, Westminster, CO.

Presented in part at the 40th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, June 5-8, 2004; 26th Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 3-6, 2003; and Eighth Annual Scientific Meeting of the Society for Neuro-Oncology, Keystone, CO, November 13-16, 2003.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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