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Temozolomide in Advanced Neuroendocrine Neoplasms: Pharmacological and Clinical Aspects
Attikon Univ Hosp, Hematol Oncol Unit, Dept Internal Med 4, GR-12462 Athens, Greece..
Natl Tech Univ Athens, Dept Pathophysiol, Endocrine Unit, Athens, Greece..
Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine oncology.
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2015 (English)In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 101, no 4, 274-288 p.Article in journal (Refereed) PublishedText
Abstract [en]

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 CP-nnethylguanineDNA 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. 

Place, publisher, year, edition, pages
2015. Vol. 101, no 4, 274-288 p.
Keyword [en]
Neuroendocrine neoplasms, Pancreatic neuroendocrine neoplasms, Neuroendocrine carcinomas, Ki-67 labelling index, Progression-free survival
National Category
Cancer and Oncology
URN: urn:nbn:se:uu:diva-269787DOI: 10.1159/000430816ISI: 000358103400002PubMedID: 25924937OAI: oai:DiVA.org:uu-269787DiVA: diva2:885377
Available from: 2015-12-18 Created: 2015-12-18 Last updated: 2015-12-18Bibliographically approved

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