Efaproxiral: a novel radiation sensitiser.
Efaproxiral (RSR13) is a synthetic allosteric modifier of haemoglobin that reduces its oxygen binding affinity. By facilitating the release of oxygen from haemoglobin, efaproxiral causes an increase in whole blood P 50 (partial pressure of oxygen which results in 50% haemoglobin saturation) and an increase in the PO2 (partial pressure of oxygen) in the tissue. The therapeutic strategy of enhancing oxygen unloading from haemoglobin to tissue emulates and amplifies physiological tissue oxygenation and can enhance the oxygenation of hypoxic tumours. Since hypoxia is known to decrease the effectiveness of radiation therapy, the use of efaproxiral as a radiation sensitiser may be advantageous. Unlike previous radiation sensitisers, efaproxiral does not need to enter the cancer cells to increase radiosensitivity. Phase I-III trial data have defined the safety profile and dosing of the drug, with the potential benefit for extended survival.
Suh
John H
JH
Brain Tumour Institute, Department of Radiation Oncology, T28 Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA. suh@radonc.ccf.org
D000814:Aniline Compounds / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D017024:Chemotherapy, Adjuvant / Q000379:methods; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D006454:Hemoglobins / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006801:Humans; D007262:Infusions, Intravenous; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D015337:Multicenter Studies as Topic; D010100:Oxygen / Q000097:blood / Q000627:therapeutic use; D010313:Partial Pressure; D011422:Propionates / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*
D000814:Aniline Compounds; D006454:Hemoglobins; D011422:Propionates; D011838:Radiation-Sensitizing Agents; C067396:efaproxiral; D010100:Oxygen