Selecting patients for cytotoxic therapies in gastroenteropancreatic neuroendocrine tumors

Centro de Oncologia, Hospital Sírio Libanês, Rua Dona Adma Jafet 90, São Paulo, SP, CEP 01308-050, Brazil. Electronic address: .
Best practice & research. Clinical gastroenterology (Impact Factor: 3.48). 12/2012; 26(6):843-54. DOI: 10.1016/j.bpg.2012.12.001
Source: PubMed


Gastroenteropancreatic neuroendocrine tumours (GEP-NET) have heterogenic clinical presentations. The majority of GEP-NET tumours have an indolent behaviour, but patients will eventually develop symptoms of tumour progression or hormone secretion that may require systemic medical interventions. Cytotoxic chemotherapy has been tested in GEP-NETs since the 80s, but treatment recommendations are controversial in many instances. Patient selection is mandatory for optimal use of chemotherapy. Important prognostic factors such as primary tumour site, tumour differentiation, tumour staging and proliferation index have been identified and validated in retrospective and prospective series. The combination of those factors and the natural history of GEP-NET provide valuable information with respect to treatment planning. In this report we provide treatment recommendations to improve systemic therapy in patients with advanced GEP-NETs based on a comprehensive review of the literature.

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    • "A hagyományos kemoterápiás készítmények gyakoribb és súlyosabb mellékhatásai miatt nincs teljes egyetértés abban a vonatkozásban, hogy a jól differenciált (G1–G2) pancreas neuroendokrin daganatokban mikor érdemes kemoterápiás kezelést indítani. Alacsony proliferációs index esetén kemoterápiától nem várhatunk érdemi daganatellenes hatást [30]. Kemoterápia javasolható , ha 1. a szomatosztatinanalóg, illetve interferonkezelés (már) nem eredményes, 2. a daganat gyorsan növekszik, 3. nagy a tumortömeg, és a beteg ezzel összefüggésbe hozhatóan panaszos, 4. a klinikai jelek rossz prognózist sugallnak (csont-, illetve egyéb extrahepaticus áttétek mutathatók ki) [9] [12] [31] [32], továbbá, ha 5. a Ki-67-index >10% [33]. "
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    ABSTRACT: The author aims to review the established medical treatment options of neuroendocrine tumours, which have expanded greatly in recent years and present the most important aspects to be considered in planning patients' management. Medical treatment is usually considered in advanced stages of these tumours, as well as in cases of hormone overproduction. Somatostatin analogues have been known to be effective in alleviating hormone excess syndromes, especially carcinoid syndrome for the past 25 years. There is a convincing evidence that the somatostatin analogue octreotide is useful as an antitumor agent, at least in well-differentiated small intestinal neuroendocrine tumours and probably also in those of pancreatic origin. Interferons may be also used and the indications for their use may be almost the same. Optimal patient selection is mandatory for the use of cytotoxic chemotherapy. Streptozotocin- and, recently, temozolomide-based chemotherapies should be considered in progressive phases of well differentiated (G1/G2) pancreatic neuroendocrine tumours. A cisplatin-etoposide combination is the first choice for the treatment of G3 neuroendocrine carcinomas of any origin. Recently, the mammalian target of rapamycin inhibitor everolimus and the combined tyrosine kinase inhibitor sunitinib were registered for the treatment of G1/G2 pancreatic neuroendocrine tumours. The most recent drug treatment recommendations and therapeutic algorithms to improve systemic therapy in patients with neuroendocrine tumours are summarized and novel drug candidates with particular potential for future management of these tumours are outlined. Orv. Hetil., 2013, 154, 1556-1564.
    Orvosi Hetilap 09/2013; 154(39):1556-64. DOI:10.1556/OH.2013.29718
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    ABSTRACT: To review the recent advances and current controversies in patients with Zollinger-Ellison syndrome (ZES). Recent advances in the management of ZES include: improved understanding of the pathogenesis of gastrinoma and pancreatic neuroendocrine tumors, new prognostic classification systems, new diagnostic algorithms, more sensitive localization studies, new treatment strategies including improved control of gastric acid secretion and role for surgery, and new approaches to patients with advanced disease. Controversies include: the best approach to a patient with hypergastrinemia suspected of possibly having ZES, the appropriate gastrin assay to use, the role of surgery in patients with ZES, especially those with multiple endocrine neoplasia type 1, and the precise order of therapeutic modalities in the treatment of patients with advanced disease. This review updates clinicians regarding important advances and controversies required to optimally diagnose and manage patients with ZES.
    Current opinion in gastroenterology 11/2013; 29(6):650-661. DOI:10.1097/MOG.0b013e328365efb1 · 4.29 Impact Factor
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    ABSTRACT: Background We present a retrospective analysis of metronomic capecitabine in metastatic gastroenteropancreatic neuroendrocrine tumors (GEP-NETs). A review of the literature is also presented. Methods From January 2007 to December 2013, ten patients with metastatic GEP-NETs (four pancreatic and six ileal) who progressed after treatment with somatostatin analogs and other cytotoxic agents received oral capecitabine 1,500 mg/day continuously. The median patient age was 68 (range 29–82) years. The median treatment duration was 8 months. Results Five (50%) patients achieved a partial radiographic response, four (40%) showed stable disease, and one (10%) progressed. Median overall survival was 56 months. Three of the four pancreatic patients achieved a partial radiographic response that lasted for a median of 15.5 months; overall survival and progression-free survival in this subgroup was 58 and 6 months, respectively. Conclusion Data in the literature show that capecitabine has only occasionally been used as a single agent, with increased toxicity. Only one study using single-agent capecitabine reported a progression-free survival of 9.9 months and overall survival of 36.5 months, without an objective response or major toxicity. In our experience, metronomic capecitabine was well tolerated, although minor side effects may have been underestimated due to the retrospective nature of our study. This regimen also seems to be feasible in elderly people. Although high response rates and prolonged response duration indicate the potential efficacy of this treatment, our results should be interpreted cautiously because of the small number of patients involved. Capecitabine was most effective in the pancreatic subgroup, which would seem to be more sensitive to chemotherapy.
    OncoTargets and Therapy 10/2014; 7:1919-26. DOI:10.2147/OTT.S68573 · 2.31 Impact Factor
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