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Phase
II Trial of Procarbazine, Lomustine, and Vincristine as Initial Therapy for
Patients With Low-Grade Oligodendroglioma or Oligoastrocytoma: Efficacy and
Associations With Chromosomal Abnormalities
Jan
C. Buckner, Dean Gesme, Jr, Judith R. O’Fallon, Julie E. Hammack, Scott
Stafford, Paul D. Brown, Roland Hawkins, Bernd W. Scheithauer, Bradley J.
Erickson, Ralph Levitt, Edward G. Shaw, Robert Jenkins
From
the Mayo Clinic and Mayo Foundation, Rochester, MN; Cedar Rapids Oncology
Project CCOP, Cedar Rapids, IA; Ochsner CCOP, New Orleans, LA; Meritcare
Hospital CCOP, Fargo, ND; Wake Forest University, Winston-Salem, NC.Address
reprint requests to Jan C. Buckner, MD, Mayo Clinic, 200 First Street SW,
Rochester, MN 55905; email: buckner.jan@mayo.edu.
Purpose.
The purpose of this article is to determine the response rate and
toxicity of PCV administered before radiation therapy in patients
with newly diagnosed LGO/LGOA and to explore correlations between
response with 1p/19q deletions and aberrant p53 expression.
Background.
Despite prolonged survival of patients with low-grade oligodendroglioma
(LGO) and oligoastrocytoma (LGOA), the majority will succumb to
progressive disease.
Because procarbazine,
lomustine (CCNU), and vincristine (PCV) is active in patients with
recurrent LGO/LGOA, we hypothesized that it would be beneficial as
primary therapy.
Methods.
Adult patients with residual tumor on magnetic resonance imaging scan
following biopsy or subtotal resection of LGO/LGOA received up to six
cycles of PCV.
Radiation therapy (59.4 or
54.0 Gy) began within 10 weeks of completing chemotherapy or immediately
if there was evidence of tumor progression on PCV.
Tumor tissue was analyzed by
fluorescent in situ hybridization for 1p and 19q deletion and by
immunohistochemistry for p53 expression.
Results.
Eight of 28 (29%) and 13 of 25 (52%) eligible patients demonstrated
tumor regression as assessed by the treating physician and a blinded
central neuroradiology reviewer, respectively.
Myelosuppression was the
predominant toxicity.
Loss of 1p and 19q
were associated with LGO but not LGOA (P = .009), were inversely associated
with p53 detection, and were not associated with response to
PCV (possibly because of the small sample size).
Conclusion.
PCV produces tumor regressions in a meaningful proportion of patients
with LGO/LGOA.
Toxicity, especially
myelosuppression, is significant.
Loss of 1p and 19q seems
limited to patients with pure LGO and is inversely related to p53
alterations.
©
2003 American
Society for Clinical Oncology
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