Phase III study of efaproxiral as an adjunct to whole-brain radiation therapy for brain metastases.
OBJECTIVE
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).


METHODS
Patients with brain metastases from solid tumors and a Karnofsky performance score of > or = 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.


CONCLUSIONS
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.
Suh
John H
JH
Cleveland Clinic Foundation, Brain Tumor Institute, Department of Radiation Oncology, Cleveland, OH 44195, USA. suhj@ccf.org
Stea
Baldassarre
B
Nabid
Abdenour
A
Kresl
John J
JJ
Fortin
André
A
Mercier
Jean-Philippe
JP
Senzer
Neil
N
Chang
Eric L
EL
Boyd
Adam P
AP
Cagnoni
Pablo J
PJ
Shaw
Edward
E
D000328:Adult; D000368:Aged; D000814:Aniline Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000556:secondary* / Q000628:therapy*; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology / Q000628:therapy; D015687:Cell Hypoxia; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011422:Propionates / Q000009:adverse effects / Q000627:therapeutic use*; D011836:Radiation Tolerance; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*
D000814:Aniline Compounds; D011422:Propionates; D011838:Radiation-Sensitizing Agents; C067396:efaproxiral