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An intergroup randomized controlled clinical trial (RCT) of chemotherapy plus
radiation (RT) versus RT alone for pure and mixed anaplastic oligodendrogliomas:
Initial report of RTOG 94-02
G. Cairncross, W. Seiferheld, E. Shaw, R. Jenkins, B. Scheithauer, D. Brachman,
J. Buckner, K. Fink, L. Souhami, W. Curran
University of Calgary, Calgary, AB, Canada;
American College of Radiology, Philadelphia, PA; Wake Forest University School
of Medicine, Winston-Salem, NC; Mayo Clinic, Rochester, MN; Foundation for
Cancer Research, Phoenix, AZ; University of Texas Southwestern Medical Center,
Dallas, TX; McGill University, Montreal, PQ, Canada; Thomas Jefferson University
Hospital, Philadelphia, PA
Background. Anaplastic oligodendrogliomas (AOs) and anaplastic
oligoastrocytomas (AOAs) are treated with surgery and RT at diagnosis.
They also
respond to procarbazine, lomustine and vincristine (PCV), raising the
possibility that PCV plus RT at diagnosis may improve outcome.
Furthermore for
AOs, response to PCV and long survival have been associated with 1p and 19q
allelic loss.
Methods. A RCT was conducted to test whether dose-intense,
pre-RT PCV prolongs overall survival (primary endpoint) or progression-free
survival (secondary endpoint) versus RT alone.
Serious toxicity rates and
quality of life were other endpoints.
Patients with AOs or AOAs confirmed by
central review, who were age ≥18 years, had a Karnofsky score (KPS)
≥60 and consented, were study-eligible.
Tumor sections and peripheral
blood were also collected.
Results. 291 eligible patients were
randomized; 60% were male, 68% were < age 50, 88% had a resection, 90% had a
KPS ≥ 80 and 70% had an AO.
148 patients had PCV plus RT and 143 had RT
alone; the arms were balanced for prognostic factors.
Median survivals were
similar for both groups; 4.8 years for PCV plus RT and 4.5 years for RT (HR
1.04, 95% CI 0.74-1.45; p=0.830).
Progression-free survival tended to be longer
after combined treatment; 2.6 years for PCV plus RT versus 1.9 years for RT (HR
1.34, 95% CI 1.00-1.80; p=0.053).
During PCV, 95 patients had grade 3 or 4
toxicity and one died.
Grade 3 and 4 RT toxicities were infrequent in both
groups.
Tissues were available on 206 tumors; 92 (46%) had 1p and 19q loss.
Irrespective of treatment, patients whose tumors lacked 1p and 19q lived longer
than other patients; median survival not reached versus 2.8 years (HR 0.31, 95%
CI 0.20-0.48; p<0.001).
Longer follow-up is needed to ascertain
treatment-specific outcomes for cases with 1p and 19q loss.
Conclusions.
Pre-RT PCV does not impart a survival advantage for histologically-defined AOs
and AOAs, but may prolong progression-free survival at the expense of greater
acute toxicity.
As reported, 1p and 19q loss is a powerful prognostic marker in
oligodendroglial tumors.
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_19-00437,00.asp
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