A phase II trial of primary temozolomide in patients with grade III oligodendroglial brain tumors.
Glial tumors with oligodendroglial components are considered chemo-responsive. Forty newly diagnosed patients (11 anaplastic oligodendrogliomas [OD] and 29 anaplastic oligoastrocytomas [OA]) were enrolled into this multicenter, open-label, single-arm Phase II trial of first-line temozolomide (200 mg/m(2) on days 1-5 every 4 weeks for 6 cycles). The primary endpoint was 6-month progression-free survival (PFS) with response rate (RR), median PFS, and median overall survival (OS) as secondary endpoints. Of 39 evaluable patients at the 6-month time point (median follow-up, 34 months), 6-month PFS was 77% (95% confidence interval [CI], 74.5%-79.3%). There were 15 complete responses (CRs, 38%), 6 partial responses (PRs, 15%), and 9 disease stabilization (23%). The median PFS was 21 months (95% CI, 3-39 months), and the median OS was 43 months (95% CI, 20-66 months). Chromosome 1p/19q codeletions were seen in 47% (18 of 38) of the patients, and O-6-methylguanine-DNA-methyltransferase (MGMT) methylation was seen in 48% (10 of 21) of the patients. All patients with OD showed MGMT methylation and most (71%) had chromosome 1p/19q codeletions. Conversely, fewer patients with OA showed MGMT methylation (23%) or had chromosome 1p/19q codeletions (31%). The presence of either 1p/19q codeletion or MGMT methylation was associated with increased RR at 6 months but not with improved PFS or OS. Only 18% of the patients (7 of 40) experienced treatment-related grade 3/4 toxicities. This regimen was active and well tolerated. These data add to the growing body of data showing that primary chemotherapy may be an acceptable alternative to radiotherapy for patients with gliomas containing oligodendroglial histology.
Gan
Hui K
HK
Departments of Medical Oncology, Austin Health, Melbourne, Victoria, Australia. hui.gan@ludwig.edu.au
Rosenthal
Mark A
MA
Dowling
Anthony
A
Kalnins
Renate
R
Algar
Elizabeth
E
Wong
Nicholas
N
Benson
Angela
A
Woods
Anne-Marie
AM
Cher
Lawrence
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D017353:Gene Deletion; D006801:Humans; D053208:Kaplan-Meier Estimate; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009837:Oligodendroglioma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000077204:Temozolomide; D025521:Tumor Suppressor Proteins / Q000235:genetics; D055815:Young Adult
D000970:Antineoplastic Agents; D025521:Tumor Suppressor Proteins; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D000077204:Temozolomide
Nucleic Acids Res. 2007;35(6):e41
17289753
J Clin Oncol. 2006 Jun 20;24(18):2707-14
16782910
J Neurooncol. 2009 Mar;92(1):57-63
19011763
N Engl J Med. 2005 Mar 10;352(10):997-1003
15758010
Acta Neuropathol. 2007 Aug;114(2):97-109
17618441
J Clin Oncol. 1990 Jul;8(7):1277-80
2358840
Eur J Cancer. 2006 Oct;42(15):2499-503
16914310
J Clin Oncol. 2006 Jun 20;24(18):2715-22
16782911
J Clin Oncol. 2008 Sep 1;26(25):4189-99
18757334
N Engl J Med. 2005 Mar 10;352(10):987-96
15758009
J Clin Oncol. 2006 Oct 10;24(29):4746-53
16954518
Crit Rev Oncol Hematol. 2008 Jun;66(3):262-72
18272388
Neuro Oncol. 2009 Apr;11(2):167-75
18779504
Arch Pathol Lab Med. 2007 Feb;131(2):242-51
17284109
Cancer. 1997 Apr 1;79(7):1381-93
9083161
Int J Cancer. 2005 Jan 20;113(3):379-85
15455350
J Neuropathol Exp Neurol. 2001 Aug;60(8):808-16
11487055
J Neurooncol. 2006 Sep;79(2):153-7
16855865