J Cancer 2014; 5(8):628-632. doi:10.7150/jca.9409

Research Paper

Topotecan Monotherapy in Heavily Pretreated Patients with Progressive Advanced Stage Neuroendocrine Carcinomas

Ingrid Holst Olsen1,2,4,5,6✉, Ulrich Knigge2,5,6, Birgitte Federspiel3,6, Carsten Palnæs Hansen2,6, Anna Skov2, Andreas Kjær4,5,6, Seppo W. Langer1,6

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;
3. Depts of Pathology 5442, 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.

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.

Material and Methods: Retrospective analysis of 22 patients with disseminated and progressive neuroendocrine carcinomas (Ki67>20%, G3) successively treated with oral topotecan 2.3 mg/m2 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%).

Conclusion: Topotecan monotherapy shows modest anti-tumor activity in heavily treated patients with progressive disseminated G3 neuroendocrine carcinomas.

Keywords: neuroendocrine carcinomas, chemotherapy, topotecan.

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How to cite this article:
Olsen IH, Knigge U, Federspiel B, Hansen CP, Skov A, Kjær A, Langer SW. Topotecan Monotherapy in Heavily Pretreated Patients with Progressive Advanced Stage Neuroendocrine Carcinomas. J Cancer 2014; 5(8):628-632. doi:10.7150/jca.9409. Available from http://www.jcancer.org/v05p0628.htm