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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

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.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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