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

被引：9

作者：

Berardi, Rossana ^{[1
]}

Torniai, Mariangela ^{[1
]}

Pusceddu, Sara ^{[2
]}

Spada, Francesca ^{[3
]}

Ibrahim, Toni ^{[4
]}

Brizzi, Maria Pia ^{[5
]}

Antonuzzo, Lorenzo ^{[6
,7
]}

Ferolla, Piero ^{[8
]}

Panzuto, Francesco ^{[9
]}

Silvestris, Nicola ^{[10
]}

Partelli, Stefano ^{[11
,12
]}

Ferretti, Benedetta ^{[13
]}

Freddari, Federica ^{[14
]}

Gucciardino, Calogero ^{[15
]}

Testa, Enrica ^{[16
]}

Concas, Laura ^{[2
]}

Murgioni, Sabina ^{[3
]}

Bongiovanni, Alberto ^{[4
]}

Zichi, Clizia ^{[5
]}

Riva, Nada ^{[4
]}

Rinzivillo, Maria ^{[9
]}

Brunetti, Oronzo ^{[10
]}

Giustini, Lucio ^{[15
]}

Di Costanzo, Francesco ^{[6
]}

Delle Fave, Gianfranco ^{[9
]}

Fazio, Nicola ^{[3
]}

De Braud, Filippo ^{[2
]}

Falconi, Massimo ^{[11
,12
]}

Cascinu, Stefano ^{[1
,17
]}

机构：

[1] Univ Politecn Marche, Clin Oncol Med, AOU Osped Riuniti, Ancona, Italy

[2] Fdn IRCCS Ist Tumori, Med Oncol 1, ENETS Ctr Excellence, Milan, Italy

[3] IEO, Unit Gastrointestinal Med Oncol & Neuroendocrine, Milan, Italy

[4] Ist Sci Romagnolo Studio & Cura Tumori IRST IRCCS, Osteoncol & Rare Tumors Ctr, Meldola, Italy

[5] AOU San Luigi, Oncol Med, Orbassano, TO, Italy

[6] Azienda Opedaliero Univ Careggi, SC Oncol Med, Florence, Italy

[7] Univ Siena, Doctorate Course Genet Oncol & Clin Med, Siena, Italy

[8] Umbria Reg Canc Network, Multidisciplinary NET Grp, Perugia, Italy

[9] Sapienza Univ Rome, St Andrea Hosp, Digest & Liver Dis, Rome, Italy

[10] Natl Canc Inst Giovanni Paolo II, Med Oncol Unit, Bari, Italy

[11] Univ Politecn Marche, Chirurg Pancreas, AOU Osped Riuniti, Ancona, Italy

[12] Univ Vita & Salute, Chirurg Pancreas, Osped San Raffaele IRCCS, Milan, Italy

[13] Osped San Severino, Oncol Med, San Severino Marche, MC, Italy

[14] Osped Senigallia, Oncol Med, Senigallia, Italy

[15] Osped Fermo, Oncol Med, Fermo, Italy

[16] Osped Urbino, Oncol Med, Urbino, Italy

[17] Univ Modena & Reggio Emilia, Oncol Med, Modena, Italy

来源：

CANCER MEDICINE | 2017年 / 6卷 / 07期

关键词：

Everolimus; mTOR inhibitor; pancreatic neuroendocrine tumors; targeted therapy; MTOR PATHWAY; SOLID TUMORS; INHIBITOR; PROLIFERATION; ACTIVATION; EXPRESSION; MANAGEMENT; TARGET; AKT;

D O I：

10.1002/cam4.1028

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 55years) 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 <= 3000mg (Group A; n = 68) and CD > 3000mg (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 24months 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.

引用

页码：1493 / 1499

页数：7

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