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Phase III Trial of Chemotherapy Plus
Radiotherapy Compared With Radiotherapy Alone for Pure and Mixed
Anaplastic Oligodendroglioma: Intergroup Radiation Therapy Oncology
Group Trial 9402
Gregory Cairncross,
Brian Berkey, Edward Shaw, Robert
Jenkins, Bernd Scheithauer, David Brachman,
Jan Buckner, Karen Fink, Luis Souhami,
Normand Laperierre, Minesh Mehta, Walter
Curran
From the University of Calgary,
Calgary, Alberta; McGill University, Montreal, Quebec; University of
Toronto, Toronto, Ontario, Canada; American College of Radiology;
Thomas Jefferson University Medical Center, Philadelphia, PA; Wake
Forest University Medical Center, Winston-Salem, NC; Mayo Clinic,
Rochester, MN; Foundation for Cancer Research, Phoenix, AZ; University
of Texas Southwestern Medical Center, Dallas, TX; and the University
of Wisconsin, Madison, WI.
Address reprint requests to Gregory Cairncross, MD, Foothills Medical
Centre, Department of Clinical Neurosciences, 1403 29th St NW,
Calgary, Alberta, T2N 2T9, Canada; e-mail: jgcairnx{at}ucalgary.ca.
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Purpose. Anaplastic
oligodendroglioma (AO) and anaplastic oligoastrocytoma (AOA)
are treated with surgery and radiotherapy (RT) at diagnosis, but
they also respond to procarbazine, lomustine, and vincristine (PCV),
raising the possibility that early chemotherapy will improve
survival.
Furthermore, better outcomes in AO have been associated
with 1p and 19q allelic loss.
Patients and Methods.
Patients with AO and AOA were randomly assigned to PCV chemotherapy
followed by RT versus postoperative RT alone.
The primary end point was overall survival.
The status of 1p and 19q alleles was assessed by
fluorescence in situ hybridization.
Results. Two hundred
eighty-nine eligible patients were randomly assigned to
either PCV plus RT (n = 147) or RT alone (n = 142).
At progression, 80% of patients randomly assigned to RT had
chemotherapy.
With 3-year follow-up on most patients, the median survival
times were similar (4.9 years after PCV plus RT v
4.7 years after RT alone; hazard ratio [HR] = 0.90; 95% CI,
0.66 to 1.24; P = .26).
Progression-free survival time favored PCV plus RT (2.6 years
v 1.7 years for RT alone; HR = 0.69; 95% CI, 0.52 to 0.91;
P = .004), but 65% of patients experienced grade 3 or 4
toxicity, and one patient died.
Patients with tumors lacking 1p and 19q (46%) compared with
tumors not lacking 1p and 19q had longer median survival
times (> 7 v 2.8 years, respectively; P 
.001); longer progression-free survival was most apparent in
this subset.
Conclusion. For patients
with AO and AOA, PCV plus RT does not prolong survival.
Longer progression-free survival after PCV plus RT is associated with
significant toxicity.
Tumors lacking 1p and 19q alleles are less aggressive or
more responsive or both.
Supported by National Cancer
Institute Grants No. U10 CA21661 and U10 CA32115 to the
Radiation Therapy Oncology Group; U10 CA25224 to the North
Central Cancer Treatment Group; CA23318, CA66636, and
CA2115 to the Eastern Cooperative Oncology Group; and U10
CA37422 to Community Clinical Oncology Programs.
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