Phase III Study of Efaproxiral As an
Adjunct to Whole-Brain Radiation Therapy for Brain Metastases
John H. Suh, Baldassarre
Stea, Abdenour Nabid, John J. Kresl, André
Fortin, Jean-Philippe Mercier, Neil Senzer,
Eric L. Chang, Adam P. Boyd, Pablo J.
Cagnoni, Edward Shaw
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: firstname.lastname@example.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
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
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.
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.