title: Low dose DTIC is effective and safe in pretreated patients with well differentiated neuroendocrine tumors.
abstract: Streptozocin (STZ) based chemotherapy is recommended for patients with metastatic pancreatic neuroendocrine tumors (pNET). Temozolomide as mono- or combination therapy has been suggested to be a promising alternative. However, the treatment is costly and not approved for the treatment of pNETs. Dacarbazine (DTIC) shares the active metabolite with temozolomide and is broadly available at a low cost. The aim of this study was a retrospective evaluation of the efficacy and tolerability of a lower dose DTIC-regimen in patients with progressive advanced NETs.
  
  
  
  We retrospectively analyzed 75 patients with NETs predominantly of pancreatic origin treated at our center between 1998 and 2013. 650 mg/m(2) of DTIC were administered intravenously over 60 min every 4 weeks. Morphological response was assessed according to RECIST1.1 criteria. The median progression free survival (PFS) was calculated using Kaplan-Meier and Cox regression methods, respectively. Univariate analyses of possible prognostic markers were performed.
  
  
  
  The objective response rate (ORR) was 27 % for the entire cohort and 32 % in 50 pNET patients, respectively. Stable disease (SD) was documented in 29 patients (39 %). Median PFS (mPFS) in patients receiving DTIC was 7 months (3.9-10; 95 % confidence interval). Radiological and biochemical response were the only significant prognostic markers for longer PFS in univariate analysis. Treatment was well tolerated. Nausea was the most common side effect (31 %), only one case (1.3 %) of grade 3 toxicity (vomiting) occurred.
  
  
  
  Low dose DTIC chemotherapy is an effective and well-tolerated treatment option in patients with progressive well differentiated neuroendocrine neoplasms, especially of pancreatic origin.
authors.affiliation: Department of Gastroenterology, University Hospital Marburg, Baldinger Strasse, D35043, Marburg, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Mueller
authors.affiliation: Department of Gastroenterology, University of Halle, Ernst-Grube-Straße 40, D 06120, Halle, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Krug
authors.affiliation: Department of Gastroenterology, University Hospital Marburg, Baldinger Strasse, D35043, Marburg, Germany.
authors.forename: Moushumee
authors.initials: M
authors.lastname: Majumder
authors.affiliation: Department of Gastroenterology, University Hospital Marburg, Baldinger Strasse, D35043, Marburg, Germany. sprengea@uni-marburg.de.
authors.forename: Anja
authors.initials: A
authors.lastname: Rinke
authors.affiliation: Department of Gastroenterology, University Hospital Marburg, Baldinger Strasse, D35043, Marburg, Germany.
authors.forename: Thomas Matthias
authors.initials: TM
authors.lastname: Gress
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000627:therapeutic use; D003606:Dacarbazine / Q000008:administration & dosage* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000188:drug therapy*; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine
keywords: Chemotherapy; Dacarbazine; Neuroendocrine tumor; Objective response; Prognostic markers