A phase II trial of primary temozolomide in patients with grade III oligodendroglial brain tumors.

Abstract

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.

• Authors: Hui K Gan, Mark A Rosenthal, Anthony Dowling, Renate Kalnins, Elizabeth Algar, Nicholas Wong, Angela Benson, Anne-Marie Woods, Lawrence Cher
• Journal: Neuro-oncology (Neuro Oncol) Vol. 12 Issue 5 Pg. 500-7 (May 2010) ISSN: 1523-5866 [Electronic] England
• PMID: 20406900 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Tumor Suppressor Proteins
• Dacarbazine
• DNA Modification Methylases
• MGMT protein, human
• DNA Repair Enzymes
• Temozolomide

Topics

• Adolescent
• Adult
• Aged
• Antineoplastic Agents (therapeutic use)
• Brain Neoplasms (drug therapy, genetics, pathology)
• Chromosomes, Human, Pair 1 (genetics)
• Chromosomes, Human, Pair 19 (genetics)
• DNA Methylation
• DNA Modification Methylases (genetics)
• DNA Repair Enzymes (genetics)
• Dacarbazine (analogs & derivatives, therapeutic use)
• Disease-Free Survival
• Female
• Gene Deletion
• Humans
• Kaplan-Meier Estimate
• Loss of Heterozygosity
• Male
• Middle Aged
• Oligodendroglioma (drug therapy, genetics, pathology)
• Temozolomide
• Tumor Suppressor Proteins (genetics)
• Young Adult