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.
OBJECTIVE
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).


CONCLUSIONS
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.
Buckner
Jan C
JC
Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA. buckner_jan@mayo.edu
Gesme
Dean
D
O'Fallon
Judith R
JR
Hammack
Julie E
JE
Stafford
Scott
S
Brown
Paul D
PD
Hawkins
Roland
R
Scheithauer
Bernd W
BW
Erickson
Bradley J
BJ
Levitt
Ralph
R
Shaw
Edward G
EG
Jenkins
Robert
R
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001254:Astrocytoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008130:Lomustine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009837:Oligodendroglioma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011344:Procarbazine / Q000627:therapeutic use*; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D014750:Vincristine / Q000627:therapeutic use*
D011344:Procarbazine; D014750:Vincristine; D008130:Lomustine