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Efaproxiral
red blood cell concentration predicts efficacy in patients with brain
metastases
B Stea1,
E Shaw2, T Pintér3, J Hackman4,
M Craig4, J May4, R P Steffen4
and J H Suh5
1Department of Radiation
Oncology, The University of Arizona Health Sciences Center, 1501 North
Campbell Avenue, Tucson, AZ 85724, USA. 2Radiation Oncology
Department, Wake Forest University School of Medicine, Medical Center
Boulevard, Winston-Salem, NC 27157, USA. 3Department of
Oncology, Petz Alaldár Hospital of Gyor-Moson-Sopron County,
Zrinyi.u.13, Gyor H-9024, Hungary. 4Allos Therapeutics
Inc., 11080 CirclePoint Road, Suite 200, Westminster, CO 80020, USA. 5Cleveland
Clinic Foundation, Department of Radiation Oncology, Brain Tumor
Institute, T28, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Correspondence to: Dr B Stea, E-mail: bstea@azcc.arizona.edu.
Received 1 March 2006; revised 18 April 2006; accepted 19 April 2006.
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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 x 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.
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