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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.


Posted on: 06/08/2004

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.

Meeting: 2004 ASCO Annual Meeting
Category: Central Nervous System Tumors
SubCategory: CNS Tumors

Abstract No: 1500
Author(s): 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 ¡Ý18 years, had a Karnofsky score (KPS) ¡Ý60 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 ¡Ý 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.

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