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

Rossana Berardi, Mariangela Torniai, Sara Pusceddu, Francesca Spada, Toni Ibrahim, Maria Pia Brizzi, Lorenzo Antonuzzo, Piero Ferolla, Francesco Panzuto, Nicola Silvestris, Stefano Partelli, Benedetta Ferretti, Federica Freddari, Calogero Gucciardino, Enrica Testa, Laura Concas, Sabina Murgioni, Alberto Bongiovanni, Clizia Zichi, Nada RivaMaria Rinzivillo, Oronzo Brunetti, Lucio Giustini, Francesco Di Costanzo, Gianfranco Delle Fave, Nicola Fazio, Filippo De Braud, Massimo Falconi, Stefano Cascinu

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)1493-1499
Number of pages7
JournalCancer Medicine
Issue number7
Publication statusPublished - Jul 2017


  • Journal Article


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