Chemotherapy is considered “state of the art” for the treatment of poorly differentiated neuroendocrine neoplasms. Unfortunately, there is no standard effective post-first-line treatment for relapsing high-grade gastroenteropancreatic neuroendocrine neoplasms. We report the case of a patient with a gastric neuroendocrine carcinoma stage IV, with massive gastrointestinal bleeding at diagnosis. After the first line of platin-based chemotherapy a major tumoral response was documented, but the patient relapsed after 4 months. A second line of chemotherapy treatment was given, with the FOLFOX regimen, and the patient has been free of progression for almost 2 years. There is no second-line standard treatment accepted for this type of carcinoma, but 5-fluorouracil combined with oxaliplatin showed interesting antitumor activity.
Keywords
Carcinoma, Neuroendocrine, Stomach Neoplasms, Neoplasm Metastases, Medical Oncology
References
YaoJC, HassanM, PhanA, et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008;26(18):3063-72. [PMID:18565894] [https://doi.org/10.1200/JCO.2007.15.4377].
ÖbergK, KniggeU, KwekkeboomD, PerrenA. Neuroendocrine gastro-entero-pancreatic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23(Suppl 7):vii124-30. [PMID:22997445]
Delle FaveG, O′'TooleD, SundinA, et al. ENETS Consensus Conference participants: ENETS consensus guidelines update for gastroduodenal neuroendocrine neoplasms. Neuroendocrinology. 2016;103(2):119-24. [PMID:26784901] [https://doi.org/10.1159/000443168].
RindiG, ArnoldR, BosmanFT, et al. Nomenclature and classification of neuroendocrine neoplasms of the digestive system. In: BosmanFT, CarneiroF, HrubanRH, et al., editors. WHO classification of tumors of the digestive system. Lyon: IARC; 2010. p. 13-145.
PapeUF, JannH, Muller-NordhornJ, et al. Prognostic relevance of a novel TNM classification system for upper gastroenteropancreatic neuroendocrine tumors. Cancer. 2008;113(2):256-65. [PMID:18506737] [https://doi.org/10.1002/cncr.23549].
BongiovanniA, RivaN, RicciM, et al. First-line chemotherapy in patients with metastatic gastroenteropancreatic neuroendocrine carcinoma. Onco Targets Ther. 2015;8:3613-9. [PMID:26664145] [https://doi.org/10.2147/OTT.S91971].
KimHK, HaSY, LeeJ, et al. The impact of pathologic differentiation (well/poorly) and the degree of Ki-67 index in patients with metastatic WHO grade 3 GEP-NECs. Oncotarget. 2017;8(43):73974-80. [PMID:29088761]
SorbyeH, WelinS, LangerSW, et al. Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO grade 3): the NORDIC NEC study. Ann Oncol. 2013;24(1):152-60. [PMID:22967994] [https://doi.org/10.1093/annonc/mds276].
MitryE, BaudinE, DucreuxM, et al. Treatment of poorly differentiated neuroendocrine tumours with etoposide and cisplatin. Br J Cancer. 1999;81(8):1351-5. [PMID:10604732] [https://doi.org/10.1038/sj.bjc.6690325].
FazioN, MilioneM. Heterogeneity of grade 3 gastroenteropancreatic neuroendocrine carcinomas: new insights and treatment implications. Cancer Treat Rev. 2016;50:61-7. [PMID:27636009] [https://doi.org/10.1016/j.ctrv.2016.08.006].
HenticO, HammelP, CouvelardA, et al. FOLFIRI regimen: an effective second-line chemotherapy after failure of etoposide-platinum combination in patients with neuroendocrine carcinomas grade 3. Endocr Relat Cancer. 2012;19(6):751-7. [PMID:22940375] [https://doi.org/10.1530/ERC-12-0002].
HadouxJ, MalkaD, PlanchardD, et al. Post-first line FOLFOX chemotherapy in Grade 3 neuroendocrine carcinoma. Endocr Relat Cancer. 2015;22(3):289-98. [PMID:25770151] [https://doi.org/10.1530/ERC-15-0075].
SpadaF, AntonuzzoL, MarconciniR, et al. Oxaliplatin-based chemotherapy in advanced neuroendocrine tumors: clinical outcomes and preliminary correlation with biological factors. Neuroendocrinology. 2016;103(6):806-14. [PMID:26789262] [https://doi.org/10.1159/000444087].
WelinS, SorbyeH, SebjornsenS, KnappskogS, BuschC, ObergK. Clinical effect of temozolomide-based chemotherapy in poorly differentiated endocrine carcinoma after progression on first-line chemotherapy. Cancer. 2011;117(20):4617-22. [PMID:21456005] [https://doi.org/10.1002/cncr.26124].