title: Streptozocin-Based Chemotherapy in Patients with Advanced Neuroendocrine Neoplasms--Predictive and Prognostic Markers for Treatment Stratification.
abstract: OBJECTIVE
  Chemotherapy with streptozocin (STZ) in combination with 5-FU or doxorubicin (Dox) represents a standard of care for patients with metastatic pancreatic neuroendocrine neoplasms (pNEN). However, predictive markers for patient selection are still missing. The aim of this study was a retrospective evaluation of the clinicopathological characteristics of pNEN patients receiving STZ-based chemotherapies and to identify predictive and prognostic markers.
  
  
  METHODS
  We retrospectively analyzed 77 patients treated at our center between 1995 and 2013. The median overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan-Meier and Cox regression methods, respectively. Uni- and multivariate analyses were performed.
  
  
  RESULTS
  The median PFS (mPFS) in patients receiving STZ/5-FU/Dox was 16 months with a median OS (mOS) of 28 months. Objective response rate (ORR) and disease control rate (DCR) were 34% and 72%, respectively. Biochemical response and positive octreotide scintigraphy predicted objective response. Univariate analysis revealed Ki-67 > 10% and the absence of biochemical or objective response by imaging as independent risk factors for shorter PFS. Additionally, performance status (PS) and resection of the primary tumor were observed to influence mOS. Treatment was well tolerated with less than 10% grade 3 and 4 toxicities.
  
  
  CONCLUSIONS
  STZ-based chemotherapy is an effective and well-tolerated treatment option in patients with well differentiated neuroendocrine neoplasms. Positive octreotide scintigraphy and biochemical response predict objective response.
authors.affiliation: Department of Gastroenterology, University of Marburg, Marburg, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Krug
authors.affiliation: Department of Gastroenterology, University of Marburg, Marburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Boch
authors.affiliation: Institute of Medical Biometry, University of Marburg, Marburg, Germany.
authors.forename: Hanna
authors.initials: H
authors.lastname: Daniel
authors.affiliation: Institute of Pathology, University of Marburg, Marburg, Germany.
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Nimphius
authors.affiliation: Department of Gastroenterology, University of Marburg, Marburg, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Müller
authors.affiliation: Department of Gastroenterology and Hepatology, University of Halle, Halle, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Michl
authors.affiliation: Department of Gastroenterology, University of Marburg, Marburg, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Rinke
authors.affiliation: Department of Gastroenterology, University of Marburg, Marburg, Germany.
authors.forename: Thomas Matthias
authors.initials: TM
authors.lastname: Gress
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D018579:Patient Selection; D012189:Retrospective Studies; D012449:Safety; D013311:Streptozocin / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D013311:Streptozocin