Safety profile of efaproxiral (RSR13), a novel radiation sensitizer, in patients undergoing radiation therapy

Abstract

3090 Background: Tumor hypoxia is known to decrease radiation sensitivity of solid tumors. RSR13, a novel radiation sensitizer, is an allosteric modifier of hemoglobin. RSR13 reduces the oxygen-binding affinity of hemoglobin to facilitate the release of oxygen, leading to an increase in tumor oxygenation. Methods: A total of 538 patients across phase 1 through phase 3 clinical trials have received at least 1 dose of RSR13 as sole adjunct to radiation therapy (RT). Patients were dosed daily up to 100 mg/kg/d RSR13, 5 days a week for up to 32 doses, immediately prior to RT. Due to the pharmacodynamic effect of RSR13, and to maximize oxygen saturation, all patients received supplemental oxygen during RSR13 and RT treatments. Results: Eight treatment-emergent adverse events have been identified as components of the RSR13 safety profile: nausea/vomiting, headache, hypoxemia (hypoxia), hypotension/dizziness, infusion symptoms, rash/allergic reaction, anemia, and renal dysfunction. The majority of the hypoxemia events were asymptomatic, consisted of low pulse oximeter (SpO2) measurements alone, and were treated with increased supplemental oxygen (increased duration or flow) only. Non-hypoxemia events were typically treated with supportive care (eg, hydration, antihistamines, or antiemetics). Overall 11% of the patients treated in these studies developed a Serious Adverse Event related to RSR13. Conclusions: The use of RSR13 was well tolerated in patients with various solid tumors receiving RT. Events of the RSR13 safety profile were typically reversible and managed with supportive care alone. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Allos Therapeutics, Inc. Allos Therapeutics, Inc. Allos Therapeutics, Inc. Allos Therapeutics, Inc.