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RTOG 0118: A Phase III Study of
Conventional Radiation Therapy Alone vs. Conventional Radiation
Therapy Plus Thalidomide for Multiple Brain Metastases
J. P. Knisely, B. A. Berkey, A.
Chakravarti, W. A. Yung, W. J. Curran, H. I. Robins, B. Movsas, D. G.
Brachman, R. H. Henderson, M. P. Mehta
Yale Univ and Yale Cancer Ctr, New
Haven, CT; Radiation Therapy Oncology Group, Philadelphia, PA; MA Gen
Hosp, Boston, MA; M.D. Anderson Cancer Ctr, Houston, TX; Thomas
Jefferson Univ Hosp, Philadelphia, PA; Univ of Wisconsin, Madison, WI;
Fox Chase Cancer Ctr, Philadelphia, PA; Arizona Oncology Services,
Phoenix, AZ; Univ of Florida Shands Cancer Ctr, Jacksonville, FL
Background.
Thalidomide was selected by the RTOG for evaluation in combination
with cranial irradiation (WBRT) for brain metastases because of its
potent antiangiogenic and immunomodulatory activity.
Methods. Patients with
multiple brain metastases or metastases not eligible for radiosurgery
due to size or location and Zubrod 0-1 were enrolled and stratified by
RPA class and whether chemotherapy was planned after WBRT.
Arm 1 patients were treated with 15
fractions of WBRT (2.5 Gray per fraction, 37.5 Gy total dose); arm 2
patients received the same WBRT and oral thalidomide.
Thalidomide was started with WBRT
at 200 mg po qhs and escalated as tolerated.
The study was designed to enroll
332 patients and have an 80% power to detect a 35% increase in median
survival with an overall Type I error of 0.05, using a one sided
log-rank test.
Early stopping guidelines were to
be invoked if either the log-rank test’s p value was <0.0077 in
favor of thalidomide or if the conditional, statistical power of
detecting the hypothesized benefit was less than 15%.
Results. At the time of
the pre-planned blinded analysis, 168 patients were enrolled and 149
were analyzed.
There were 87 deaths reported at
that time.
Follow-up was 0.3-15.9 months
(median 2.4 months).
Median survivals for arm 1 and 2
were 3.6 and 4.4 months.
Arm 1 had 3 deaths and arm 2 had 2
deaths from causes known to be possible thalidomide toxicities.
The one sided log-rank test’s p
value was 0.44, and the conditional power was <1%.
It was concluded that observing a
treatment difference was very unlikely, and the study was closed to
new patient entries.
Conclusions. Thalidomide
does not improve survival in patients receiving WBRT for multiple
brain metastases.
This trial was supported by
the NCI & Celgene.
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