Efaproxiral red blood cell concentration predicts efficacy in patients with brain metastases

B. Stea, E. Shaw, T. Pintér, J. Hackman, M. Craig, J. May, R. P. Steffen, J. H. Suh

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Efaproxiral (Efaproxyn™, RSR13), a synthetic allosteric modifier of haemoglobin (Hb), decreases Hb-oxygen (O2) binding affinity and enhances oxygenation of hypoxic tumours during radiation therapy. This analysis evaluated the Phase 3, Radiation Enhancing Allosteric Compound for Hypoxic Brain Metastases; RT-009 (REACH) study efficacy results in relation to efaproxiral exposure (efaproxiral red blood cell concentration (E-RBC) and number of doses). Recursive partitioning analysis Class I or II patients with brain metastases from solid tumours received standard whole-brain radiation therapy (3 Gy/fraction × 10 days), plus supplemental O2 (4 l/min), either with efaproxiral (75 or 100 mg/kg daily) or without (control). Efaproxiral red blood cell concentrations were linearly extrapolated to all efaproxiral doses received. Three patient populations were analysed: (1) all eligible, (2) non-small-cell lung cancer (NSCLC) as primary cancer, and (3) breast cancer primary. Efficacy endpoints were survival and response rate. Brain metastases patients achieving sufficient E-RBC (≥483 μg/ml) and receiving at least seven of 10 efaproxiral doses were most likely to experience survival and response benefits. Patients with breast cancer primary tumours generally achieved the target efaproxiral exposure and therefore gained greater benefit from efaproxiral treatment than NSCLC patients. This analysis defined the efaproxiral concentration-dependence in survival and response rate improvement, and provided a clearer understanding of efaproxiral dosing requirements.

Original languageEnglish
Pages (from-to)1777-1784
Number of pages8
JournalBritish Journal of Cancer
Volume94
Issue number12
DOIs
Publication statusPublished - Jun 19 2006

Fingerprint

Erythrocytes
Neoplasm Metastasis
Brain
Non-Small Cell Lung Carcinoma
efaproxiral
Hemoglobins
Radiotherapy
Survival Rate
Neoplasms
Blood Cell Count
Radiation
Breast Neoplasms
Oxygen
Survival

Keywords

  • Brain metastases
  • Breast cancer
  • Efaproxiral
  • Radiation sensitiser
  • RSR13
  • Whole-brain radiation therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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.

In: British Journal of Cancer, Vol. 94, No. 12, 19.06.2006, p. 1777-1784.

Research output: Contribution to journalArticle

Stea, B, Shaw, E, Pintér, T, Hackman, J, Craig, M, May, J, Steffen, RP & Suh, JH 2006, 'Efaproxiral red blood cell concentration predicts efficacy in patients with brain metastases', British Journal of Cancer, vol. 94, no. 12, pp. 1777-1784. https://doi.org/10.1038/sj.bjc.6603169
Stea, B. ; Shaw, E. ; Pintér, T. ; Hackman, J. ; Craig, M. ; May, J. ; Steffen, R. P. ; Suh, J. H. / Efaproxiral red blood cell concentration predicts efficacy in patients with brain metastases. In: British Journal of Cancer. 2006 ; Vol. 94, No. 12. pp. 1777-1784.
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