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Standard whole brain radiation therapy (WBRT) with supplemental oxygen (O2),
with or without RSR13 (efaproxiral) in patients with brain metastases: Results
of the randomized REACH (RT-009) study
J. Suh, B. Stea, A. Nabid, J. Kresl, A. Fortin, J. P. Mercier, N. Senzer, E.
Chang, J. B. Holz, E. Shaw
Cleveland Clinic, Cleveland, OH; University of Arizona Health
Sciences Center, Tuscon, AZ; Centre Hospitalier Universitarie de Sherbrooke,
Sherbrooke, PQ, Canada; Foundation for Cancer Research and Education, Phoenix,
AZ; Hotel-Dieu de Quebec du CHUQ, Quebec City, PQ, Canada; Hopital
Maisonneuve-Rosemont, Montreal, PQ, Canada; US Oncology Research, Inc, Dallas,
TX; University of Texas, M. D. Anderson Cancer Center, Houston, TX; Allos
Therapeutics, Inc, Westminster, CO; Wake Forest University School of Medicine,
Winston-Salem, NC
Background.
Brain metastases represent a common cause of morbidity and
mortality among cancer pts.
The effectiveness of WBRT as primary therapy for brain metastases is limited by
tissue hypoxia, which has been shown to cause radioresistance in solid
tumors.
RSR13 (efaproxiral) is a novel radiation sensitizer that acts as an allosteric
modifier of hemoglobin, facilitates O2 release and decreases tissue
hypoxia.
Methods.
A randomized, open-label Phase 3 study was conducted comparing
RSR13 and WBRT to WBRT alone in pts. with newly diagnosed brain metastases from
various solid tumors.
In the RSR13 arm (n=271), pts. received RSR13 (75-100 mg/kg/d, IV) plus O2
followed by WBRT (30 Gy, 3 Gy/d x 10 days).
In the Control arm (n=267), pts. received WBRT plus O2.
The primary endpoint was survival.
Secondary endpoints were RR in the brain, TTP, cause of death and QoL.
Results.
A total of 538 pts. were enrolled over 29 months at 82 sites in
12 countries.
In the overall study population (n=538), the RSR13 arm demonstrated a 17.6%
improvement in median survival time (MST) over the Control arm (5.26 mo vs. 4.47
mo; p=0.17).
The survival benefit for RSR13 was statistically significant in a Cox multiple
regression model (Hazard Ratio 0.78 [95% CI 0.64, 0.94], p=0.010).
Pts. with breast cancer or NSCLC (n=414) receiving RSR13 had a 32.4% increase in
MST vs. Control (5.91 vs. 4.47 mo; p=0.12).
In pts. with breast cancer (n=115) the MST almost doubled in those who received
RSR13 vs. Control (8.67 vs. 4.57 mo; p=0.006).
The percentage of breast cancer pts. with stable/improved KPS at 3 months was
significantly higher in the RSR13 arm (35% vs 18%, p=0.001).
Related SAEs that are part of the RSR13 safety profile occurred in 7% of
pts.
The most common RSR13-related SAE was hypoxemia (3.4 %), which is dose-dependent
and effectively managed with increased supplemental O2.
Conclusions.
The addition of RSR13 to WBRT was well tolerated and led to
a 22% reduction in the risk of death for all pts.
A near doubling in MST and significant improvement in QoL were observed in pts.
with brain metastases from breast cancer.
Copyright 2004 American Society of Clinical Oncology All rights
reserved worldwide.
Source: http://www.asco.org/ac/1,1003,_12-002636-00_18-0026-00_19-00263,00.asp
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