An algorithm for chemotherapy treatment of recurrent glioma patients after temozolomide failure in the general oncology setting

Cancer Chemother Pharmacol. 2011 May;67(5):971-83. doi: 10.1007/s00280-011-1617-9. Epub 2011 Mar 27.

Abstract

Purpose: The standard therapy for newly diagnosed malignant gliomas comprises surgery, radiotherapy, and commonly temozolomide chemotherapy. For recurrent or progressive disease after temozolomide failure, there is no consensus and only limited options for chemotherapy.

Methods: We reviewed the English literature for phase II trials of therapies for recurrent malignant glioma conducted between January 2000 and September 2010. The search was supplemented by a review of articles published prior to 2000 on chemotherapy regimens that had shown activity on recurrent gliomas.

Results: To guide practice in the general oncology setting, an algorithm was constructed according to the activity of the reported chemotherapies at the time of writing. Some molecular studies performed on tumor tissue may help guide the selection of chemotherapy. Methylated MGMT in tumor tissue correlates with increased sensitivity to alkylating agents such as fotemustine or other nitrosoureas. Depending on MGMT status and bone marrow reserve, treatment with fotemustine, bevacizumab, bevacizumab with irinotecan, or cis-retinoic acid (cRA), might be of value.

Conclusion: Unfortunately, progress in the development of new and more effective chemotherapy agents has been very limited and leaves the clinician treating high-grade glioma patients at relapse with few good options. The suggested algorithm is our objective evaluation of the currently existing knowledge. Hopefully, the ongoing phase II and III trials will provide us the needed chemotherapy agents in the years to come.

Publication types

  • Review

MeSH terms

  • Algorithms
  • Angiogenesis Inhibitors / therapeutic use*
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / genetics
  • Clinical Trials, Phase II as Topic
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / therapeutic use
  • Genotype
  • Glioma / drug therapy*
  • Glioma / genetics
  • Humans
  • Molecular Targeted Therapy
  • Neoplasm Recurrence, Local / drug therapy*
  • Temozolomide
  • Treatment Failure

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents, Alkylating
  • Dacarbazine
  • Temozolomide