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

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%) 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 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 well-tolerated. Oral and IV Etop schedules are associated with comparable toxicity; activity should be compared in larger cohorts.

• Authors: 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
• Journal: Neuroendocrinology (Neuroendocrinology) Vol. 109 Issue 2 Pg. 100-112 ( 2019) ISSN: 1423-0194 [Electronic] Switzerland
• PMID: 30703770 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 S. Karger AG, Basel.

Chemical References

• Etoposide
• Carboplatin

Topics

• Administration, Intravenous
• Administration, Oral
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Carboplatin (administration & dosage, adverse effects)
• Carcinoma, Neuroendocrine (drug therapy, pathology)
• Cell Differentiation
• Etoposide (administration & dosage, adverse effects)
• Female
• Gastrointestinal Neoplasms (drug therapy, pathology)
• Humans
• Male
• Middle Aged
• Neuroendocrine Tumors (drug therapy, pathology)
• Retrospective Studies
• Treatment Outcome
• Young Adult