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Chemical Compound Review

Efaproxyn     2-[4-[(3,5-dimethylphenyl) carbamoylmethyl]...

Synonyms: Efaproxiral, RSR-13, RSR-56, RSR13, CHEMBL18901, ...
 
 
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Disease relevance of RQ3

  • The low incidence of grade 3 to 4 toxicities suggests that the use of efaproxiral instead of a cytotoxic agent, as a radiation sensitizer, may be advantageous [1].
  • We conducted a phase II multicenter study that assessed the efficacy and safety of efaproxiral when administered with thoracic radiation therapy (TRT), following induction chemotherapy, for treatment of locally advanced non-small-cell lung cancer (NSCLC) [1].
  • Grade 3 to 4 toxicities related to efaproxiral that occurred in more than one patient included transient hypoxemia (19%), radiation pneumonitis (11%), and fatigue (4%) [1].
  • Brain metastases patients achieving sufficient E-RBC (> or =483 microg/ml) and receiving at least seven of 10 efaproxiral doses were most likely to experience survival and response benefits [2].
  • Patients with breast cancer primary tumours generally achieved the target efaproxiral exposure and therefore gained greater benefit from efaproxiral treatment than NSCLC patients [2].
 

High impact information on RQ3

 

Chemical compound and disease context of RQ3

 

Biological context of RQ3

 

Anatomical context of RQ3

 

Analytical, diagnostic and therapeutic context of RQ3

  • Increased oxygenation of intracranial tumors by efaproxyn (efaproxiral), an allosteric hemoglobin modifier: In vivo EPR oximetry study [8].
  • RESULTS: Treatment arm, Karnofsky Performance Status, presence or absence of liver metastases, and primary site were all determinants of response at the 3-month follow-up visit, with patients in the efaproxiral arm experiencing a 67% greater odds of response at this visit (p = 0.02) [3].
  • Further investigation and results from the ongoing clinical trials will help to define the role of efaproxiral in clinical practice [4].

References

  1. 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. 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, A.P., Cagnoni, P.J., Curran, W.J. J. Clin. Oncol. (2005) [Pubmed]
  2. Efaproxiral red blood cell concentration predicts efficacy in patients with brain metastases. Stea, B., Shaw, E., Pintér, T., Hackman, J., Craig, M., May, J., Steffen, R.P., Suh, J.H. Br. J. Cancer (2006) [Pubmed]
  3. Whole-brain radiotherapy with or without efaproxiral for the treatment of brain metastases: Determinants of response and its prognostic value for subsequent survival. Stea, B., Suh, J.H., Boyd, A.P., Cagnoni, P.J., Shaw, E. Int. J. Radiat. Oncol. Biol. Phys. (2006) [Pubmed]
  4. Efaproxiral: a radiation enhancer used in brain metastases from breast cancer. Charpentier, M.M. The Annals of pharmacotherapy. (2005) [Pubmed]
  5. Using exposure-response and biomarkers to streamline early drug development. Venitz, J. Ernst Schering Res. Found. Workshop (2007) [Pubmed]
  6. Efaproxiral (RSR13) plus oxygen breathing increases the therapeutic ratio of carboplatin in EMT6 mouse mammary tumors. Donnelly, E.T., Liu, Y., Rockwell, S. Exp. Biol. Med. (Maywood) (2006) [Pubmed]
  7. Cerebral metastases--a therapeutic update. Cavaliere, R., Schiff, D. Nature clinical practice. Neurology. (2006) [Pubmed]
  8. Increased oxygenation of intracranial tumors by efaproxyn (efaproxiral), an allosteric hemoglobin modifier: In vivo EPR oximetry study. Hou, H., Khan, N., O'Hara, J.A., Grinberg, O.Y., Dunn, J.F., Abajian, M.A., Wilmot, C.M., Demidenko, E., Lu, S., Steffen, R.P., Swartz, H.M. Int. J. Radiat. Oncol. Biol. Phys. (2005) [Pubmed]
 
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