Carboplatin in combination with oral or intravenous etoposide for extra-pulmonary, poorly-differentiated neuroendocrine carcinomas

Melissa Frizziero, Francesca Spadaro, Angela Lamarca, Zoe Kordatou, Jorge Barriuso, Christina Nuttall, Mairead Mcnamara, Richard Hubner, Wasat Mansoor, Prakash Manoharan, Nicola Fazio, Juan Valle

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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 retrospectively collected 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%) 3rd-line. 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% versus 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 versus 6.2 months, p=0.179), although there was a trend towards shorter OS (8.9 versus 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% versus 1.7%, p=0.04). Conclusions: CarboEtop for advanced EP-PD-NEC is active, effective and well-tolerated. Oral- and IV-Etop schedules are associated with comparable toxicity; activity should be compared in larger cohorts.
Original languageEnglish
Early online date21 Jan 2019
Publication statusPublished - Aug 2019


  • carboplatin-etoposide
  • extra-pulmonary neuroendocrine carcinoma
  • oral etoposide
  • intravenous etoposide

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre


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