Post-first-line FOLFOX chemotherapy for grade 3 neuroendocrine carcinoma

Endocr Relat Cancer. 2015 Jun;22(3):289-98. doi: 10.1530/ERC-15-0075. Epub 2015 Mar 13.


There is no standard for second-line chemotherapy in poorly differentiated grade 3 neuroendocrine carcinoma (G3-NEC) patients. We analyzed the antitumor efficacy of 5-fluorouracil and oxaliplatin (FOLFOX) chemotherapy in this population. A single-center retrospective analysis of consecutive G3-NEC patients treated with FOLFOX chemotherapy after failure of a cisplatinum-based regimen between December 2003 and June 2012 was performed. Progression-free survival (PFS), overall survival (OS), response rate, and safety were assessed according to RECIST 1.1 and NCI.CTC v4 criteria. Twenty consecutive patients were included (seven males and 13 females; median age 55; range 23-87 years) with a performance status of 0-1 in 75% of them. Primary location was gastroenteropancreatic in 12, thoracic in four, other in two, and unknown in two patients. There were 12 (65%) large-cell and 7 (30%) small-cell G3-NEC tumors, and 1 (5%) unknown. All patients had distant metastases. Twelve (60%) patients received FOLFOX as second-line treatment and 8 (40%) as third-line treatment or later and the median number of administered cycles was 6 (range 3-14). The median follow-up was 19 months. Median PFS was 4.5 months. Among the 17 evaluable patients, five partial responses (29%), six stable diseases (35%), and six progressive diseases (35%) were observed. Median OS was 9.9 months. Main Grade 3-4 toxicities were neutropenia (35%), thrombopenia (20%), nausea/vomiting (10%), anemia (10%), and elevated liver transaminases (10%). Our results indicate that the FOLFOX regimen could be considered as a second-line option in poorly differentiated G3-NEC patients after cisplatinum-based first-line treatment but warrant further confirmation in future larger prospective studies.

Keywords: FOLFOX; grade 3; neuroendocrine carcinoma; oxaliplatin; poorly differentiated neuroendocrine tumor; second-line chemotherapy.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Neuroendocrine / drug therapy*
  • Carcinoma, Neuroendocrine / pathology
  • Disease-Free Survival
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Leucovorin / administration & dosage
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Organoplatinum Compounds / administration & dosage
  • Retrospective Studies
  • Young Adult


  • Organoplatinum Compounds
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Folfox protocol