Low-dose chemotherapy in combination with COX-2 inhibitors and PPAR-gamma agonists in recurrent high-grade gliomas - a phase II study

Oncology. 2007;73(1-2):21-5. doi: 10.1159/000120028. Epub 2008 Mar 10.

Abstract

Objectives: Combined treatment approaches targeting tumor as well as other cells contributing to tumor progression may control chemorefractory malignancies.

Methods: A phase II trial was initiated to analyze the activity of continuously administered pioglitazone and rofecoxib combined with low-dose chemotherapy (capecitabine or temozolomide) in patients with high-grade gliomas (glioblastoma or anaplastic glioma).

Results: Fourteen patients were evaluable for response and toxicity. Major side effects were palmoplantar erythema, edema and motor neuropathy grade 3. Disease stabilizations lasting longer than 3 months were noted in 4 of 14 patients (29%). Clinical responses did not correspond to immunohistochemical staining for cyclooxygenase 2, peroxisome proliferator-activated receptor-gamma and CD31.

Discussion: The study demonstrates that this novel regimen is moderately active and well tolerated in patients with high-grade gliomas. As a comparably small proportion of patients responded, the regimen might only be suitable for a subset of highly selected patients.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Apoptosis / drug effects
  • Brain Neoplasms / blood supply
  • Brain Neoplasms / chemistry
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology*
  • Capecitabine
  • Cyclooxygenase 2 Inhibitors / adverse effects
  • Cyclooxygenase 2 Inhibitors / therapeutic use*
  • Dacarbazine / administration & dosage
  • Dacarbazine / analogs & derivatives
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Drug Administration Schedule
  • Edema / chemically induced
  • Efferent Pathways / drug effects
  • Erythema / chemically induced
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / analogs & derivatives
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma / drug therapy
  • Glioma / blood supply
  • Glioma / chemistry
  • Glioma / drug therapy*
  • Glioma / pathology*
  • Humans
  • Immunohistochemistry
  • Lactones / administration & dosage
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / pathology
  • Neovascularization, Pathologic / prevention & control
  • PPAR gamma / agonists*
  • Pioglitazone
  • Predictive Value of Tests
  • Quality of Life
  • Sulfones / administration & dosage
  • Temozolomide
  • Thiazolidinediones / administration & dosage
  • Treatment Outcome

Substances

  • Cyclooxygenase 2 Inhibitors
  • Lactones
  • PPAR gamma
  • Sulfones
  • Thiazolidinediones
  • rofecoxib
  • Deoxycytidine
  • Capecitabine
  • Dacarbazine
  • Fluorouracil
  • Pioglitazone
  • Temozolomide