Carboplatin in Combination with Oral or Intravenous Etoposide for Extra-Pulmonary, Poorly-Differentiated Neuroendocrine Carcinomas

Melissa Frizziero, Francesca Spada, Angela Lamarca, Zoe Kordatou, Jorge Barriuso, Christina Nuttall, Mairéad G. McNamara, Richard A. Hubner, Wasat Mansoor, Prakash Manoharan, Nicola Fazio, Juan W. Valle

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Abstract

Background: Carboplatin-etoposide (CarboEtop) is a 1st-line option for patients with advanced extra-pulmonary (EP), poorly-differentiated (PD) neuroendocrine carcinoma (NEC). Different schedules are used in clinical practice and randomised evidence is lacking. Objectives: To provide real-life outcomes of carboplatin combined with oral or intravenous (IV) etoposide (Etop) in advanced EP-PD-NEC, from 2 specialist centres. Methods: Activity/efficacy/toxicity data of CarboEtop were collected retrospectively and analysed. Results: We identified 113 patients; median age: 65.8 years; male: 64%; gastro-entero-pancreatic origin: 54%; stage IV: 90%; median Ki-67: 70%; median follow-up: 11.5 months. A total of 123 courses of CarboEtop (oral: 45%; IV: 55%) were administered; 106 (86%) 1st-line, 16 (13%) 2nd-line, and 1 (1%) 3rdline. Disease control rate: 74.5% in 1st-line and 69.2% in 2nd/3rd-line, with no significant difference between oral and IV Etop in 1st-line (69.8 vs. 80.8%, p = 0.237). Median progression- free survival (PFS): 6.0 and 4.5 months in 1st-line and 2nd/3rd-line, respectively. Overall survival (OS): 11.5 and 12.5 months in 1st-line and 2nd/3rd-line, respectively. The schedule (oral versus IV Etop) did not impact on 1st-line PFS (5.6 vs. 6.2 months, p = 0.179), although there was a trend towards shorter OS (8.9 vs. 12.1 months, p = 0.069). Liver metastases correlated with worse 1st-line PFS (p = 0.015) and 1st-line OS (p < 0.001) on multivariable analysis. The commonest grade 3-4 adverse event was myelosuppression (49%), with comparable toxicity between oral and IV Etop, except for venous thromboembolism (12.5 vs. 1.7%, p = 0.04). Conclusions: CarboEtop for advanced EP-PD-NEC is active, effective, and welltolerated. Oral and IV Etop schedules are associated with comparable toxicity; activity should be compared in larger cohorts.

Original languageEnglish
Pages (from-to)100-112
Number of pages13
JournalNeuroendocrinology
Volume109
Issue number2
DOIs
Publication statusPublished - Aug 1 2019

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Keywords

  • Carboplatin-etoposide
  • Extra-pulmonary neuroendocrine carcinoma
  • Intravenous etoposide
  • Oral etoposide

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

Cite this

Frizziero, M., Spada, F., Lamarca, A., Kordatou, Z., Barriuso, J., Nuttall, C., McNamara, M. G., Hubner, R. A., Mansoor, W., Manoharan, P., Fazio, N., & Valle, J. W. (2019). Carboplatin in Combination with Oral or Intravenous Etoposide for Extra-Pulmonary, Poorly-Differentiated Neuroendocrine Carcinomas. Neuroendocrinology, 109(2), 100-112. https://doi.org/10.1159/000497336