title: Oxaliplatin-Based Chemotherapy in Advanced Neuroendocrine Tumors: Clinical Outcomes and Preliminary Correlation with Biological Factors.
abstract: The role of chemotherapy in low-/intermediate-grade neuroendocrine tumors (NETs) is still debated. We present the results of an Italian multicenter retrospective study evaluating activity and toxicity of oxaliplatin-based chemotherapy in patients with advanced NETs.
  
  
  
  Clinical records from 5 referral centers were reviewed. Disease control rate (DCR) corresponding to PR + SD (partial response + stable disease) at 6 months, progression-free survival (PFS), overall survival (OS) and toxicity were calculated. Ki67 labeling index, grade of differentiation and excision- repair-cross-complementing group 1 (ERCC-1) were analyzed in tissue tumor samples.
  
  
  
  Seventy-eight patients entered the study. Primary sites were: pancreas in 46, gastrointestinal in 24, lung in 19 and unknown in 10% of patients. The vast majority were G2 (2010 WHO classification). Eighty-six percent of the patients were metastatic, and 87% were pretreated and progressive to previous therapies. Sixty-five percent of the patients received capecitabine/oxaliplatin (CAPOX), 6% gemcitabine/oxaliplatin (GEMOX), and 29% leucovorin/fluorouracil/oxaliplatin (FOLFOX-6). PR occurred in 26% of the patients, half of them with pancreatic NETs, and SD in 54%. With a median follow-up of 21 months, the median PFS and OS were 8 and 32 months with 70 and 45 events, respectively. The most frequent G3 toxicities were neurological and gastrointestinal. ERCC-1 immunohistochemical overexpression was positive in 4/28 evaluated samples, with no significant correlation with clinical outcome.
  
  
  
  This analysis suggests that oxaliplatin-based chemotherapy can be active with a manageable safety profile in advanced NETs irrespective of the primary sites and tumor grade. The 80% DCR and 8-month PFS could justify a prospective study in NETs with intermediate biological characteristics, especially with pancreatic primary tumors.
authors.affiliation: Gastrointestinal Medical Oncology and Neuroendocrine Tumors Unit, European Institute of Oncology, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Spada
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Antonuzzo
authors.forename: Riccardo
authors.initials: R
authors.lastname: Marconcini
authors.forename: Davide
authors.initials: D
authors.lastname: Radice
authors.forename: Andrea
authors.initials: A
authors.lastname: Antonuzzo
authors.forename: Sergio
authors.initials: S
authors.lastname: Ricci
authors.forename: Francesco
authors.initials: F
authors.lastname: Di Costanzo
authors.forename: Annalisa
authors.initials: A
authors.lastname: Fontana
authors.forename: Fabio
authors.initials: F
authors.lastname: Gelsomino
authors.forename: Gabriele
authors.initials: G
authors.lastname: Luppi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Nobili
authors.forename: Salvatore
authors.initials: S
authors.lastname: Galdy
authors.forename: Chiara Alessandra
authors.initials: CA
authors.lastname: Cella
authors.forename: Angelica
authors.initials: A
authors.lastname: Sonzogni
authors.forename: Eleonora
authors.initials: E
authors.lastname: Pisa
authors.forename: Massimo
authors.initials: M
authors.lastname: Barberis
authors.forename: Nicola
authors.initials: N
authors.lastname: Fazio
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D001685:Biological Factors / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000188:drug therapy; D004268:DNA-Binding Proteins / Q000378:metabolism; D004720:Endonucleases / Q000378:metabolism; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000401:mortality; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D000077150:Oxaliplatin; D010190:Pancreatic Neoplasms / Q000188:drug therapy; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001685:Biological Factors; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C071447:ERCC1 protein, human; D004720:Endonucleases