Oxaliplatin-Based Chemotherapy in Advanced Neuroendocrine Tumors: Clinical Outcomes and Preliminary Correlation with Biological Factors

Francesca Spada, Lorenzo Antonuzzo, Riccardo Marconcini, Davide Radice, Andrea Antonuzzo, Sergio Ricci, Francesco Di Costanzo, Annalisa Fontana, Fabio Gelsomino, Gabriele Luppi, Elisabetta Nobili, Salvatore Galdy, Chiara Alessandra Cella, Angelica Maria Sonzogni, Eleonora Pisa, Massimo Barberis, Nicola Fazio

Research output: Contribution to journalArticle

Abstract

Purpose: The role of chemotherapy in low/intermediate grade neuroendocrine tumors (NETs) is still debated. We present the results of an Italian multicenter retrospective study, evaluating activity and toxicity of oxaliplatin-based chemotherapy in patients with advanced NETs. Methods: Clinical records from 5 referral centers were reviewed. Disease control rate (DCR) corresponding to PR+SD (partial response + stable disease) at 6 months, progression free survival (PFS), overall survival (OS) and toxicity were calculated. Ki67 labeling-index, grade of differentiation and excision-repair-cross-complementing group-1 (ERCC-1) were analyzed in tissue tumor samples. Results: Seventy-eight patients entered the study. Primary sites were: pancreas in 46, gastrointestinal in 24, lung in 19, and unknown in 10% patients. The vast majority were G2 (2010 WHO classification). Eighty-six percent of patients were metastatic, 87% pretreated and progressive to previous therapies. 65% patients received capecitabine/oxaliplatin (CAPOX), 6% gemcitabine/oxaliplatin (GEMOX), 29% leucovorin/fluorouracil/oxaliplatin (FOLFOX-6). Partial response occurred in 26% patients, half of them with pancreatic NETs (PNETs), and SD in 54%. With 21 months median follow-up, the median PFS and OS were 8 and 32 months with 70 and 45 events, respectively. The most frequent G3 toxicities were neurological and gastrointestinal. ERCC-1 immunohistochemical over-expression was positive in 4/28 evaluated samples, with no significant correlation with clinical outcome. Conclusion: This analysis suggests that oxaliplatin-based chemotherapy can be active with a manageable safety profile in advanced NETs irrespective of the primary sites and tumor grade. The 80% DCR and 8 months PFS could justify a prospective study in NETs with intermediate biological characteristics, especially with pancreatic primary. © 2016 S. Karger AG, Basel

Original languageEnglish
JournalNeuroendocrinology
DOIs
Publication statusAccepted/In press - Jan 21 2016

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oxaliplatin
Neuroendocrine Tumors
Biological Factors
Drug Therapy
Disease-Free Survival
gemcitabine
DNA Repair
Survival
Leucovorin
Fluorouracil
Multicenter Studies
Pancreas
Neoplasms
Referral and Consultation
Retrospective Studies

ASJC Scopus subject areas

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

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Oxaliplatin-Based Chemotherapy in Advanced Neuroendocrine Tumors : Clinical Outcomes and Preliminary Correlation with Biological Factors. / Spada, Francesca; Antonuzzo, Lorenzo; Marconcini, Riccardo; Radice, Davide; Antonuzzo, Andrea; Ricci, Sergio; Di Costanzo, Francesco; Fontana, Annalisa; Gelsomino, Fabio; Luppi, Gabriele; Nobili, Elisabetta; Galdy, Salvatore; Cella, Chiara Alessandra; Sonzogni, Angelica Maria; Pisa, Eleonora; Barberis, Massimo; Fazio, Nicola.

In: Neuroendocrinology, 21.01.2016.

Research output: Contribution to journalArticle

Spada, Francesca ; Antonuzzo, Lorenzo ; Marconcini, Riccardo ; Radice, Davide ; Antonuzzo, Andrea ; Ricci, Sergio ; Di Costanzo, Francesco ; Fontana, Annalisa ; Gelsomino, Fabio ; Luppi, Gabriele ; Nobili, Elisabetta ; Galdy, Salvatore ; Cella, Chiara Alessandra ; Sonzogni, Angelica Maria ; Pisa, Eleonora ; Barberis, Massimo ; Fazio, Nicola. / Oxaliplatin-Based Chemotherapy in Advanced Neuroendocrine Tumors : Clinical Outcomes and Preliminary Correlation with Biological Factors. In: Neuroendocrinology. 2016.
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abstract = "Purpose: The role of chemotherapy in low/intermediate grade neuroendocrine tumors (NETs) is still debated. We present the results of an Italian multicenter retrospective study, evaluating activity and toxicity of oxaliplatin-based chemotherapy in patients with advanced NETs. Methods: Clinical records from 5 referral centers were reviewed. Disease control rate (DCR) corresponding to PR+SD (partial response + stable disease) at 6 months, progression free survival (PFS), overall survival (OS) and toxicity were calculated. Ki67 labeling-index, grade of differentiation and excision-repair-cross-complementing group-1 (ERCC-1) were analyzed in tissue tumor samples. Results: Seventy-eight patients entered the study. Primary sites were: pancreas in 46, gastrointestinal in 24, lung in 19, and unknown in 10{\%} patients. The vast majority were G2 (2010 WHO classification). Eighty-six percent of patients were metastatic, 87{\%} pretreated and progressive to previous therapies. 65{\%} patients received capecitabine/oxaliplatin (CAPOX), 6{\%} gemcitabine/oxaliplatin (GEMOX), 29{\%} leucovorin/fluorouracil/oxaliplatin (FOLFOX-6). Partial response occurred in 26{\%} patients, half of them with pancreatic NETs (PNETs), and SD in 54{\%}. With 21 months median follow-up, the median PFS and OS were 8 and 32 months with 70 and 45 events, respectively. The most frequent G3 toxicities were neurological and gastrointestinal. ERCC-1 immunohistochemical over-expression was positive in 4/28 evaluated samples, with no significant correlation with clinical outcome. Conclusion: This analysis suggests that oxaliplatin-based chemotherapy can be active with a manageable safety profile in advanced NETs irrespective of the primary sites and tumor grade. The 80{\%} DCR and 8 months PFS could justify a prospective study in NETs with intermediate biological characteristics, especially with pancreatic primary. {\circledC} 2016 S. Karger AG, Basel",
author = "Francesca Spada and Lorenzo Antonuzzo and Riccardo Marconcini and Davide Radice and Andrea Antonuzzo and Sergio Ricci and {Di Costanzo}, Francesco and Annalisa Fontana and Fabio Gelsomino and Gabriele Luppi and Elisabetta Nobili and Salvatore Galdy and Cella, {Chiara Alessandra} and Sonzogni, {Angelica Maria} and Eleonora Pisa and Massimo Barberis and Nicola Fazio",
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T1 - Oxaliplatin-Based Chemotherapy in Advanced Neuroendocrine Tumors

T2 - Clinical Outcomes and Preliminary Correlation with Biological Factors

AU - Spada, Francesca

AU - Antonuzzo, Lorenzo

AU - Marconcini, Riccardo

AU - Radice, Davide

AU - Antonuzzo, Andrea

AU - Ricci, Sergio

AU - Di Costanzo, Francesco

AU - Fontana, Annalisa

AU - Gelsomino, Fabio

AU - Luppi, Gabriele

AU - Nobili, Elisabetta

AU - Galdy, Salvatore

AU - Cella, Chiara Alessandra

AU - Sonzogni, Angelica Maria

AU - Pisa, Eleonora

AU - Barberis, Massimo

AU - Fazio, Nicola

PY - 2016/1/21

Y1 - 2016/1/21

N2 - Purpose: The role of chemotherapy in low/intermediate grade neuroendocrine tumors (NETs) is still debated. We present the results of an Italian multicenter retrospective study, evaluating activity and toxicity of oxaliplatin-based chemotherapy in patients with advanced NETs. Methods: Clinical records from 5 referral centers were reviewed. Disease control rate (DCR) corresponding to PR+SD (partial response + stable disease) at 6 months, progression free survival (PFS), overall survival (OS) and toxicity were calculated. Ki67 labeling-index, grade of differentiation and excision-repair-cross-complementing group-1 (ERCC-1) were analyzed in tissue tumor samples. Results: Seventy-eight patients entered the study. Primary sites were: pancreas in 46, gastrointestinal in 24, lung in 19, and unknown in 10% patients. The vast majority were G2 (2010 WHO classification). Eighty-six percent of patients were metastatic, 87% pretreated and progressive to previous therapies. 65% patients received capecitabine/oxaliplatin (CAPOX), 6% gemcitabine/oxaliplatin (GEMOX), 29% leucovorin/fluorouracil/oxaliplatin (FOLFOX-6). Partial response occurred in 26% patients, half of them with pancreatic NETs (PNETs), and SD in 54%. With 21 months median follow-up, the median PFS and OS were 8 and 32 months with 70 and 45 events, respectively. The most frequent G3 toxicities were neurological and gastrointestinal. ERCC-1 immunohistochemical over-expression was positive in 4/28 evaluated samples, with no significant correlation with clinical outcome. Conclusion: This analysis suggests that oxaliplatin-based chemotherapy can be active with a manageable safety profile in advanced NETs irrespective of the primary sites and tumor grade. The 80% DCR and 8 months PFS could justify a prospective study in NETs with intermediate biological characteristics, especially with pancreatic primary. © 2016 S. Karger AG, Basel

AB - Purpose: The role of chemotherapy in low/intermediate grade neuroendocrine tumors (NETs) is still debated. We present the results of an Italian multicenter retrospective study, evaluating activity and toxicity of oxaliplatin-based chemotherapy in patients with advanced NETs. Methods: Clinical records from 5 referral centers were reviewed. Disease control rate (DCR) corresponding to PR+SD (partial response + stable disease) at 6 months, progression free survival (PFS), overall survival (OS) and toxicity were calculated. Ki67 labeling-index, grade of differentiation and excision-repair-cross-complementing group-1 (ERCC-1) were analyzed in tissue tumor samples. Results: Seventy-eight patients entered the study. Primary sites were: pancreas in 46, gastrointestinal in 24, lung in 19, and unknown in 10% patients. The vast majority were G2 (2010 WHO classification). Eighty-six percent of patients were metastatic, 87% pretreated and progressive to previous therapies. 65% patients received capecitabine/oxaliplatin (CAPOX), 6% gemcitabine/oxaliplatin (GEMOX), 29% leucovorin/fluorouracil/oxaliplatin (FOLFOX-6). Partial response occurred in 26% patients, half of them with pancreatic NETs (PNETs), and SD in 54%. With 21 months median follow-up, the median PFS and OS were 8 and 32 months with 70 and 45 events, respectively. The most frequent G3 toxicities were neurological and gastrointestinal. ERCC-1 immunohistochemical over-expression was positive in 4/28 evaluated samples, with no significant correlation with clinical outcome. Conclusion: This analysis suggests that oxaliplatin-based chemotherapy can be active with a manageable safety profile in advanced NETs irrespective of the primary sites and tumor grade. The 80% DCR and 8 months PFS could justify a prospective study in NETs with intermediate biological characteristics, especially with pancreatic primary. © 2016 S. Karger AG, Basel

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