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

Research output: Contribution to journalArticle

141 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)106-114
Number of pages9
JournalJournal of Clinical Oncology
Volume24
Issue number1
DOIs
StatePublished - Jan 1 2006
Externally publishedYes

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Radiotherapy
Neoplasm Metastasis
Brain
Breast Neoplasms
Survival
Non-Small Cell Lung Carcinoma
efaproxiral
Radiation-Sensitizing Agents
Oxygen
Safety Management
Risk Reduction Behavior
Hemoglobins
Survival Rate
Regression Analysis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Phase III study of efaproxiral as an adjunct to whole-brain radiation therapy for brain metastases. / Suh, John H.; Stea, Baldassarre; Nabid, Abdenour; Kresl, John J.; Fortin, André; Mercier, Jean Philippe; Senzer, Neil; Chang, Eric L.; Boyd, Adam P.; Cagnoni, Pablo J.; Shaw, Edward.

In: Journal of Clinical Oncology, Vol. 24, No. 1, 01.01.2006, p. 106-114.

Research output: Contribution to journalArticle

Suh, JH, Stea, B, Nabid, A, Kresl, JJ, Fortin, A, Mercier, JP, Senzer, N, Chang, EL, Boyd, AP, Cagnoni, PJ & Shaw, E 2006, 'Phase III study of efaproxiral as an adjunct to whole-brain radiation therapy for brain metastases', Journal of Clinical Oncology, vol. 24, no. 1, pp. 106-114. https://doi.org/10.1200/JCO.2004.00.1768
Suh, John H. ; Stea, Baldassarre ; Nabid, Abdenour ; Kresl, John J. ; Fortin, André ; Mercier, Jean Philippe ; Senzer, Neil ; Chang, Eric L. ; Boyd, Adam P. ; Cagnoni, Pablo J. ; Shaw, Edward. / Phase III study of efaproxiral as an adjunct to whole-brain radiation therapy for brain metastases. In: Journal of Clinical Oncology. 2006 ; Vol. 24, No. 1. pp. 106-114.
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T1 - Phase III study of efaproxiral as an adjunct to whole-brain radiation therapy for brain metastases

AU - Suh, John H.

AU - Stea, Baldassarre

AU - Nabid, Abdenour

AU - Kresl, John J.

AU - Fortin, André

AU - Mercier, Jean Philippe

AU - Senzer, Neil

AU - Chang, Eric L.

AU - Boyd, Adam P.

AU - Cagnoni, Pablo J.

AU - Shaw, Edward

PY - 2006/1/1

Y1 - 2006/1/1

N2 - 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.

AB - 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.

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