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Cancer Med. 2017 Jul;6(7):1493-1499. doi: 10.1002/cam4.1028. Epub 2017 May 25.

Prognostic impact of the cumulative dose and dose intensity of everolimus in patients with pancreatic neuroendocrine tumors.

Author information

1
Clinica di Oncologia Medica, Università Politecnica delle Marche, AOU Ospedali Riuniti di, Ancona, Italy.
2
Medicina Oncologica 1, ENETS Center of excellence, Fondazione IRCCS Istituto Tumori, Milano, Italy.
3
Unità di Oncologia Medica Gastrointestinale e Tumori Neuroendocrini (Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors), IEO Istituto Europeo di Oncologia, Milano, Italy.
4
Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
5
Oncologia Medica, A.O.U. San Luigi, Orbassano (TO), Italy.
6
SC di Oncologia Medica, Azienda Opedaliero-Universitaria Careggi, Firenze, Italy.
7
Doctorate Course in Genetics, Oncology and Clinical Medicine, University of Siena, Siena, Italy.
8
Multidisciplinary NET Group, Umbria Regional Cancer Network, Perugia, Italy.
9
Digestive and Liver Disease, Sapienza University of Rome, Sant'Andrea Hospital, Rome, Italy.
10
Medical Oncology Unit, National Cancer Institute Giovanni Paolo II, Bari, Italy.
11
Chirurgia del Pancreas, Università Politecnica delle Marche, AOU Ospedali Riuniti di, Ancona, Italy.
12
Chirurgia del Pancreas, Ospedale San Raffaele IRCCS, Università Vita e Salute, Milano, Italy.
13
Oncologia Medica, Ospedale di San Severino, San Severino Marche (MC), Italy.
14
Oncologia Medica, Ospedale di Senigallia, Senigallia, Italy.
15
Oncologia Medica, Ospedale di Fermo, Fermo, Italy.
16
Oncologia Medica, Ospedale di Urbino, Urbino, Italy.
17
Oncologia Medica, Università di Modena e Reggio Emilia, Modena, Italy.

Abstract

The aim of this work is to assess if cumulative dose (CD) and dose intensity (DI) of everolimus may affect survival of advanced pancreatic neuroendocrine tumors (PNETs) patients. One hundred and sixteen patients (62 males and 54 females, median age 55 years) with advanced PNETs were treated with everolimus for ≥3 months. According to a Receiver operating characteristics (ROC) analysis, patients were stratified into two groups, with CD ≤ 3000 mg (Group A; n = 68) and CD > 3000 mg (Group B; n = 48). The response rate and toxicity were comparable in the two groups. However, patients in group A experienced more dose modifications than patients in group B. Median OS was 24 months in Group A while in Group B it was not reached (HR: 26.9; 95% CI: 11.0-76.7; P < 0.0001). Patients who maintained a DI higher than 9 mg/day experienced a significantly longer OS and experienced a trend to higher response rate. Overall, our study results showed that both CD and DI of everolimus play a prognostic role for patients with advanced PNETs treated with everolimus. This should prompt efforts to continue everolimus administration in responsive patients up to at least 3000 mg despite delays or temporary interruptions.

KEYWORDS:

Everolimus; mTOR inhibitor; pancreatic neuroendocrine tumors; targeted therapy

PMID:
28547856
PMCID:
PMC5504331
DOI:
10.1002/cam4.1028
[Indexed for MEDLINE]
Free PMC Article

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