Role of efaproxiral in metastatic brain tumors

Expert Review of Anticancer Therapy
Ryan H Engel, Virginia G Kaklamani

Abstract

Brain metastases from breast cancer are common and cause significant morbidity and mortality. Treatment with whole-brain radiotherapy provides a median survival of only 4-6 months. One mechanism affecting sensitivity to radiation is tumor oxygenation. Hypoxic tumor cells are more likely to be resistant to radiation and adversely affect prognosis. For nearly 70 years, all attempted modalities have failed to circumvent tumor hypoxia and increase tumor death. Abraham and colleagues developed a fibric acid derivative that would cause the displacement of oxygen from hemoglobin and improve tissue oxygenation. After modifications to enhance absorption into the red blood cell, RSR13 (efaproxiral) was developed. Efaproxiral was found to be safe and improved tumor oxygenation in preclinical studies. Early Phase I and II trials supported the earlier preclinical evidence while demonstrating that efaproxiral was safe and effective. A randomized Phase III study, Radiation Enhancing Allosteric Compounds of Hypoxic brain metastases (REACH, RT-009), failed to show a significant improvement in overall survival in all eligible patients treated with efaproxiral and whole-brain radiation. However, there was a statistically significant improvement i...Continue Reading

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Mar 20, 2014·Neuro-oncology·Alenoush VartanianGelareh Zadeh

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