Berardi Rossana, Torniai Mariangela, Pusceddu Sara, Spada Francesca, Ibrahim Toni, Brizzi Maria Pia, Antonuzzo Lorenzo, Ferolla Piero, Panzuto Francesco, Silvestris Nicola, Partelli Stefano, Ferretti Benedetta, Freddari Federica, Gucciardino Calogero, Testa Enrica, Concas Laura, Murgioni Sabina, Bongiovanni Alberto, Zichi Clizia, Riva Nada, Rinzivillo Maria, Brunetti Oronzo, Giustini Lucio, Di Costanzo Francesco, Delle Fave Gianfranco, Fazio Nicola, De Braud Filippo, Falconi Massimo, Cascinu Stefano
Clinica di Oncologia Medica, Università Politecnica delle Marche, AOU Ospedali Riuniti di, Ancona, Italy.
Medicina Oncologica 1, ENETS Center of excellence, Fondazione IRCCS Istituto Tumori, Milano, Italy.
Cancer Med. 2017 Jul;6(7):1493-1499. doi: 10.1002/cam4.1028. Epub 2017 May 25.
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.
这项工作的目的是评估依维莫司的累积剂量（CD）和剂量强度（DI）是否会影响晚期胰腺神经内分泌肿瘤（PNETs）患者的生存。116例晚期PNETs患者（62例男性和54例女性，中位年龄55岁）接受依维莫司治疗≥3个月。根据受试者工作特征（ROC）分析，患者被分为两组，CD≤3000mg（A组；n = 68）和CD>3000mg（B组；n = 48）。两组的缓解率和毒性相当。然而，A组患者比B组患者经历了更多的剂量调整。A组的中位总生存期为24个月，而B组未达到（HR：26.9；95%CI：11.0 - 76.7；P < 0.0001）。维持DI高于9mg/天的患者总生存期显著更长，且缓解率有升高趋势。总体而言，我们的研究结果表明，依维莫司的CD和DI对接受依维莫司治疗的晚期PNETs患者均具有预后作用。这应促使我们努力在反应性患者中持续给予依维莫司，直至至少3000mg，尽管可能会有延迟或暂时中断。
