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

Hui K Gan, Mark Andrew Rosenthal, Anthony J. Dowling, Renate Kalnins, Elizabeth Algar, Nicholas Wong, Angela Benson, Anne Marie Woods, Lawrence Cher

Research output: Contribution to journalArticleResearchpeer-review

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/m2 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.

Original languageEnglish
Pages (from-to)500-507
Number of pages8
JournalNeuro-Oncology
Volume12
Issue number5
DOIs
Publication statusPublished - May 2010
Externally publishedYes

Keywords

  • 19q
  • 1p
  • MGMT methylation
  • Oligodendroglial
  • Temozolomide

Cite this

Gan, Hui K ; Rosenthal, Mark Andrew ; Dowling, Anthony J. ; Kalnins, Renate ; Algar, Elizabeth ; Wong, Nicholas ; Benson, Angela ; Woods, Anne Marie ; Cher, Lawrence. / A Phase II trial of primary temozolomide in patients with grade III oligodendroglial brain tumors. In: Neuro-Oncology. 2010 ; Vol. 12, No. 5. pp. 500-507.
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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/m2 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.",
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Gan, HK, Rosenthal, MA, Dowling, AJ, Kalnins, R, Algar, E, Wong, N, Benson, A, Woods, AM & Cher, L 2010, 'A Phase II trial of primary temozolomide in patients with grade III oligodendroglial brain tumors' Neuro-Oncology, vol. 12, no. 5, pp. 500-507. https://doi.org/10.1093/neuonc/nop065

A Phase II trial of primary temozolomide in patients with grade III oligodendroglial brain tumors. / Gan, Hui K; Rosenthal, Mark Andrew; Dowling, Anthony J.; Kalnins, Renate; Algar, Elizabeth; Wong, Nicholas; Benson, Angela; Woods, Anne Marie; Cher, Lawrence.

In: Neuro-Oncology, Vol. 12, No. 5, 05.2010, p. 500-507.

Research output: Contribution to journalArticleResearchpeer-review

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