Temozolomide in Advanced Neuroendocrine Neoplasms: Pharmacological and Clinical Aspects

Anna Koumarianou, Gregory Kaltsas, Matthew H. Kulke, Kjell Oberg, Jonathan R. Strosberg, Francesca Spada, Salvatore Galdy, Massimo Barberis, Caterina Fumagalli, Alfredo Berruti, Nicola Fazio

Research output: Contribution to journalArticlepeer-review

Abstract

Alkylating agents, such as streptozocin and dacarbazine, have been reported as active in neuroendocrine neoplasms (NENs). Temozolomide (TMZ) is an oral, potentially less toxic derivative of dacarbazine, which has shown activity both as a single agent and in combination with other drugs. Nevertheless, its role in NENs has not been well defined. Several retrospective and prospective phase I-II studies have been published describing its use in a variety of NENs. In a retrospective series, the combination of capecitabine and TMZ was reported to be associated with a particularly high tumour response in pancreatic NENs as a first-line treatment. Although in NENs, determination of the O6-methylguanine-DNA methyltransferase (MGMT) status has been suggested as a predictive biomarker of response, its role still remains investigational, awaiting validation along with the establishment of the optimal detection method. Metronomic schedules have been reported to potentially overcome MGMT-related drug resistance. Toxicity is manageable if well monitored. We reviewed the literature regarding pharmacological and clinical aspects of TMZ, focusing on specific settings of NENs, different schedules, toxicity and safety profiles, and potential predictive biomarkers of response.

Original languageEnglish
Pages (from-to)274-288
Number of pages15
JournalNeuroendocrinology
Volume101
Issue number4
DOIs
Publication statusPublished - Jul 25 2015

Keywords

  • Ki-67 labelling index
  • Neuroendocrine carcinomas
  • Neuroendocrine neoplasms
  • Pancreatic neuroendocrine neoplasms
  • Progression-free survival

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

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