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According to Drugs R D. 2005;6(3):178-85. Efaproxiral  is a synthetic, small-molecule, radiation-sensitising agent being developed by Allos Therapeutics primarily for the treatment of cancer. It works by binding and allosterically stabilising deoxyhaemoglobin in hypoxic regions of tumour tissue. This increases oxygen uptake of the tumour tissue and restores its sensitivity to radiation therapy, making therapy potentially more successful. This first-of-its-class compound is particularly applicable for the treatment of certain tumour types that lack oxygen, such as brain metastases. In contrast to conventional chemotherapeutic agents or radiation sensitisers, there is no requirement for efaproxiral to be administered directly into tumours or to cross the blood-brain barrier for it to display efficacy.  Efaproxiral is under review for approval in the US and EU as an adjunct to whole-brain radiation therapy (WBRT) for the treatment of brain metastases originating from breast cancer. It is also under clinical evaluation for a variety of other cancers, including glioblastoma, non-small cell lung cancer (NSCLC) and cervical cancer.

According to wikipedia.com, Efaproxiral (INN) is an analog of the cholesterol drug bezafibrate developed for the treatment of depression, traumatic brain injury, ischemia, stroke, myocardial infarction, diabetes, hypoxia, sickle cell disease, hypercholesterolemia and as a radio sensitizer. The chemical is a propanoic acid in the class of amphipathic carboxylic acids. Most propanoic acid produced is consumed as a preservative for both animal feed and food for human consumption. One use for efaproxiral is to increase the efficacy of certain chemotherapy drugs which have reduced efficacy against hypoxic tumours, and can thus be made more effective by increased offloading of oxygen into the tumour tissues. No benefit was seen for efaproxiral in phase III clinical trials. (source: http://en.wikipedia.org/wiki/Efaproxiral).

1: Gustafsson T, Pontén F, Seeberger PH. Trimethylaluminium mediated amide bond formation in a continuous flow microreactor as key to the synthesis of rimonabant and efaproxiral. Chem Commun (Camb). 2008 Mar 7;(9):1100-2. Epub 2008 Feb 1. PubMed PMID: 18292903.

2: Scott C, Suh J, Stea B, Nabid A, Hackman J. Improved survival, quality of life, and quality-adjusted survival in breast cancer patients treated with efaproxiral (Efaproxyn) plus whole-brain radiation therapy for brain metastases.  Am J Clin Oncol. 2007 Dec;30(6):580-7. PubMed PMID: 18091051.

3: Hou H, Khan N, Grinberg OY, Yu H, Grinberg SA, Lu S, Demidenko E, Steffen RP,  Swartz HM. The effects of Efaproxyn (efaproxiral) on subcutaneous RIF-1 tumor oxygenation and enhancement of radiotherapy-mediated inhibition of tumor growth in mice. Radiat Res. 2007 Aug;168(2):218-25. PubMed PMID: 17638413.

4: Stea B, Shaw E, Pintér T, Hackman J, Craig M, May J, Steffen RP, Suh JH. Efaproxiral red blood cell concentration predicts efficacy in patients with brain metastases. Br J Cancer. 2006 Jun 19;94(12):1777-84. PubMed PMID: 16773073; PubMed Central PMCID: PMC2361352.

5: Engel RH, Kaklamani VG. Role of efaproxiral in metastatic brain tumors. Expert Rev Anticancer Ther. 2006 Apr;6(4):477-85. Review. PubMed PMID: 16613536.

6: Donnelly ET, Liu Y, Rockwell S. Efaproxiral (RSR13) plus oxygen breathing increases the therapeutic ratio of carboplatin in EMT6 mouse mammary tumors. Exp  Biol Med (Maywood). 2006 Mar;231(3):317-21. PubMed PMID: 16514179.

7: Stea B, Suh JH, Boyd AP, Cagnoni PJ, Shaw E; REACH Study Group. Whole-brain radiotherapy with or without efaproxiral for the treatment of brain metastases: Determinants of response and its prognostic value for subsequent survival. Int J  Radiat Oncol Biol Phys. 2006 Mar 15;64(4):1023-30. Epub 2006 Jan 30. PubMed PMID: 16446056.

8: Suh JH, Stea B, Nabid A, Kresl JJ, Fortin A, Mercier JP, Senzer N, Chang EL, Boyd AP, Cagnoni PJ, Shaw E. Phase III study of efaproxiral as an adjunct to whole-brain radiation therapy for brain metastases. J Clin Oncol. 2006 Jan 1;24(1):106-14. Epub 2005 Nov 28. PubMed PMID: 16314619.

9: Sneed PK. Efaproxiral: should we hold our breath? J Clin Oncol. 2006 Jan 1;24(1):13-5. Epub 2005 Nov 28. PubMed PMID: 16314614.

10: Charpentier MM. Efaproxiral: a radiation enhancer used in brain metastases from breast cancer. Ann Pharmacother. 2005 Dec;39(12):2038-45. Epub 2005 Oct 25.  Review. PubMed PMID: 16249270.

11: Choy H, Nabid A, Stea B, Scott C, Roa W, Kleinberg L, Ayoub J, Smith C, Souhami L, Hamburg S, Spanos W, Kreisman H, Boyd AP, Cagnoni PJ, Curran WJ. Phase II multicenter study of induction chemotherapy followed by concurrent efaproxiral (RSR13) and thoracic radiotherapy for patients with locally advanced non-small-cell lung cancer. J Clin Oncol. 2005 Sep 1;23(25):5918-28. PubMed PMID: 16135463.

12: Efaproxiral: GSJ 61, JP 4, KDD 86, RS 4, RSR 13. Drugs R D. 2005;6(3):178-85. Review. PubMed PMID: 15869322.

13: Hou H, Khan N, O'Hara JA, Grinberg OY, Dunn JF, Abajian MA, Wilmot CM, Demidenko E, Lu S, Steffen RP, Swartz HM. Increased oxygenation of intracranial tumors by efaproxyn (efaproxiral), an allosteric hemoglobin modifier: In vivo EPR oximetry study. Int J Radiat Oncol Biol Phys. 2005 Apr 1;61(5):1503-9. PubMed PMID: 15817356.

14: Suh JH. Efaproxiral: a novel radiation sensitiser. Expert Opin Investig Drugs. 2004 May;13(5):543-50. PubMed PMID: 15155129.

15: Shaw E, Scott C, Suh J, Kadish S, Stea B, Hackman J, Pearlman A, Murray K, Gaspar L, Mehta M, Curran W, Gerber M. RSR13 plus cranial radiation therapy in patients with brain metastases: comparison with the Radiation Therapy Oncology Group Recursive Partitioning Analysis Brain Metastases Database. J Clin Oncol. 2003 Jun 15;21(12):2364-71. PubMed PMID: 12805339.

16: Kavanagh BD, Khandelwal SR, Schmidt-Ullrich RK, Roberts JD, Shaw EG, Pearlman AD, Venitz J, Dusenbery KE, Abraham DJ, Gerber MJ. A phase I study of RSR13, a radiation-enhancing hemoglobin modifier: tolerance of repeated intravenous doses  and correlation of pharmacokinetics with pharmacodynamics. Int J Radiat Oncol Biol Phys. 2001 Mar 15;49(4):1133-9. PubMed PMID: 11240256.

17: Mackensen GB, Nellgård B, Sarraf-Yazdi S, Dexter F, Steffen RP, Grocott HP, Warner DS. Post-ischemic RSR13 amplifies the effect of dizocilpine on outcome from transient focal cerebral ischemia in the rat. Brain Res. 2000 Jan 17;853(1):15-21. PubMed PMID: 10627303.

18: Kilgore KS, Shwartz CF, Gallagher MA, Steffen RP, Mosca RS, Bolling SF. RSR13, a synthetic allosteric modifier of hemoglobin, improves myocardial recovery following hypothermic cardiopulmonary bypass. Circulation. 1999 Nov 9;100(19 Suppl):II351-6. PubMed PMID: 10567328.

19: Kleinberg L, Grossman SA, Piantadosi S, Pearlman J, Engelhard H, Lesser G, Ruffer J, Gerber M. Phase I trial to determine the safety, pharmacodynamics, and  pharmacokinetics of RSR13, a novel radioenhancer, in newly diagnosed glioblastoma multiforme. J Clin Oncol. 1999 Aug;17(8):2593-603. PubMed PMID: 10561327.

20: Sarraf-Yazdi S, Sheng H, Grocott HP, Bart RD, Pearlstein RD, Steffen RP, Warner DS. Effects of RSR13, a synthetic allosteric modifier of hemoglobin, alone and in combination with dizocilpine, on outcome from transient focal cerebral ischemia in the rat. Brain Res. 1999 May 1;826(2):172-80. PubMed PMID: 10224294.

21: Khandelwal SR, Kavanagh BD, Lin PS, Truong QT, Lu J, Abraham DJ, Schmidt-Ullrich RK. RSR13, an allosteric effector of haemoglobin, and carbogen radiosensitize FSAII and SCCVII tumours in C3H mice. Br J Cancer. 1999 Feb;79(5-6):814-20. PubMed PMID: 10070874; PubMed Central PMCID: PMC2362693.

22: Steffen RP. Effect of RSR13 on temperature-dependent changes in hemoglobin oxygen affinity of human whole blood. Adv Exp Med Biol. 1998;454:653-61. PubMed PMID: 9889946.

23: Pagel PS, Hettrick DA, Montgomery MW, Kersten JR, Warltier DC. RSR13, a synthetic allosteric modifier of hemoglobin, enhances recovery of stunned myocardium in dogs. Adv Exp Med Biol. 1998;454:527-31. PubMed PMID: 9889932.

24: Rockwell S, Kelley M. RSR13, a synthetic allosteric modifier of hemoglobin, as an adjunct to radiotherapy: preliminary studies with EMT6 cells and tumors and normal tissues in mice. Radiat Oncol Investig. 1998;6(5):199-208. PubMed PMID: 9822166.

25: Pagel PS, Hettrick DA, Montgomery MW, Kersten JR, Steffen RP, Warltier DC. RSR13, a synthetic modifier of hemoglobin-oxygen affinity, enhances the recovery  of stunned myocardium in anesthetized dogs. J Pharmacol Exp Ther. 1998 Apr;285(1):1-8. PubMed PMID: 9535987.

26: Kunert MP, Liard JF, Abraham DJ. RSR-13, an allosteric effector of hemoglobin, increases systemic and iliac vascular resistance in rats. Am J Physiol. 1996 Aug;271(2 Pt 2):H602-13. PubMed PMID: 8770102.