Up-front temozolomide in elderly patients with anaplastic oligodendroglioma and oligoastrocytoma

J Neurooncol. 2011 Feb;101(3):457-62. doi: 10.1007/s11060-010-0264-z. Epub 2010 Jun 17.

Abstract

Optimal treatment of anaplastic oligodendroglial tumors (AOT) in elderly patients is debatable. We report a retrospective study of 44 consecutive patients aged 70 years or older [median age: 74 years; median Karnofsky performance status (KPS): 70] treated with up-front chemotherapy using temozolomide (TMZ) at conventional doses until tumor progression. O(6)-methylguanine-DNA methyltransferase promoter (MGMTP) methylation was assessed in 38 patients. Of the 41 evaluable patients, partial response (PR) was seen in 13 (32%) patients, 17 (41%) patients achieved stable disease, while the disease progressed in 11 (27%) patients. Median progression-free survival (PFS) and overall survival (OS) were 6.9 and 12.4 months, respectively. Hematotoxicity grades 3-4 occurred in nine patients (20%). MGMTP was methylated in 50% of patients and was associated with both longer PFS (8.7 versus 5.7 months, P = 0.01) and longer OS (16.1 versus 12.4 months, P = 0.05). The rate of responders to chemotherapy was similar in MGMTP-methylated (38%) and in MGMTP-unmethylated patients (31%), but duration of response was significantly longer in responders with methylated MGMTP than in responders with unmethylated MGMTP (16.1 versus 9.6 months, P = 0.0004). This study demonstrates that a substantial number of elderly patients with AOT can achieve prolonged survival with up-front chemotherapy using TMZ. Further investigation is needed to determine whether this treatment is preferable to initial radiation therapy.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Alkylating / pharmacology*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • DNA Methylation*
  • DNA Modification Methylases / genetics
  • DNA Repair Enzymes / genetics
  • DNA, Neoplasm / genetics
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / pharmacology
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Oligodendroglioma / drug therapy*
  • Oligodendroglioma / genetics
  • Oligodendroglioma / pathology
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic / genetics
  • Retrospective Studies
  • Survival Rate
  • Temozolomide
  • Treatment Outcome
  • Tumor Suppressor Proteins / genetics

Substances

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