title: Topotecan monotherapy in heavily pretreated patients with progressive advanced stage neuroendocrine carcinomas.
abstract: BACKGROUND
  Neuroendocrine carcinomas (WHO grade 3) are highly aggressive tumors with an immense tendency to metastasize and with a poor prognosis. In advanced disease, there is no standard treatment beyond first-line platin/etoposide-based chemotherapy. Topotecan is widely used as second-line treatment in small cell lung cancer, which also responds markedly on first-line platin/etoposide. Hence, we investigated the feasibility of topotecan in previously treated patients with neuroendocrine carcinomas.
  
  
  METHODS
  Retrospective analysis of 22 patients with disseminated and progressive neuroendocrine carcinomas (Ki67>20%, G3) successively treated with oral topotecan 2.3 mg/m(2) d1-5 every 3 weeks. All patients had previously received treatment with carboplatin/etoposide. Demographic, clinical and pathological features were recorded. CT-evaluations according to RECIST 1.1 were performed after every three courses. Hematological toxicity was assessed by CTC-criteria.
  
  
  RESULTS
  Twenty-two eligible patients received a median of 2 courses [range1-6]. Median age: 65 years [35-77]. Male/female: 11/11. Median Ki-67 index: 95% [25-100%]. Median number previous chemotherapy regimens: 2 [1-3]. All patients were evaluable for response: Five achieved stable disease (SD) and 17 progressed (PD). The median overall survival for the 22 patients was 3.2 months and the median progression-free survival was 2.1 months. The one-year survival was 18%. There were no treatment related deaths. The treatment was well tolerated: Haematological toxicity comprised leukopenia CTC grade 3 (14%), grade 4 (9%) and thrombocytopenia grade 3 (14%).
  
  
  CONCLUSIONS
  Topotecan monotherapy shows modest anti-tumor activity in heavily treated patients with progressive disseminated G3 neuroendocrine carcinomas.
authors.affiliation: 1. Depts of Oncology 5073, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Denmark; ; 2. Depts of Surgery 2122, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Denmark; ; 4. Depts of Clinical Physiology, Nuclear Medicine & PET 4011, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Denmark; ; 5. Cluster of Molecular Imaging, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Denmark; ; 6. European NET Centre of Excellence, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Denmark.
authors.forename: Ingrid Holst
authors.initials: IH
authors.lastname: Olsen
authors.affiliation: 2. Depts of Surgery 2122, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Denmark; ; 5. Cluster of Molecular Imaging, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Denmark; ; 6. European NET Centre of Excellence, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Denmark.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Knigge
authors.affiliation: 3. Depts of Pathology 5442, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Denmark; ; 6. European NET Centre of Excellence, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Denmark.
authors.forename: Birgitte
authors.initials: B
authors.lastname: Federspiel
authors.affiliation: 2. Depts of Surgery 2122, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Denmark; ; 6. European NET Centre of Excellence, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Denmark.
authors.forename: Carsten Palnæs
authors.initials: CP
authors.lastname: Hansen
authors.affiliation: 2. Depts of Surgery 2122, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Denmark;
authors.forename: Anna
authors.initials: A
authors.lastname: Skov
authors.affiliation: 4. Depts of Clinical Physiology, Nuclear Medicine & PET 4011, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Denmark; ; 5. Cluster of Molecular Imaging, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Denmark; ; 6. European NET Centre of Excellence, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Denmark.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kjær
authors.affiliation: 1. Depts of Oncology 5073, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Denmark; ; 6. European NET Centre of Excellence, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Denmark.
authors.forename: Seppo W
authors.initials: SW
authors.lastname: Langer
keywords: chemotherapy; neuroendocrine carcinomas; topotecan.