Gambacorta Maria Antonietta, De Paoli Antonino, Lupattelli Marco, Chiloiro Giuditta, Solazzo Angela Pia, Barbaro Brunella, Alfieri Sergio, Vecchio Fabio Maria, Lenkowicz Jacopo, Navarria Francesco, Palazzari Elisa, Bertola Giulio, Frattegiani Alessandro, Minsky Bruce, Valentini Vincenzo
Polo scienze oncologiche ed ematologiche, Fondazione Policlinico Universitario Agostino Gemelli Roma, Italy.
Department of Radiotherapy, Centro di Riferimento Oncologico, Aviano, Italy.
Clin Transl Radiat Oncol. 2018 Mar 17;10:23-28. doi: 10.1016/j.ctro.2018.02.003. eCollection 2018 Mar.
The aim of this study is to evaluate the long term survival of the addition of gefitinib to chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC).
This previously published multicentre, open-label, phase I-II study, enrolled patients (pts) with LARC to receive CRT with concurrent 5-fluorouracil continuous intravenous infusion and a dose escalation of orally administered gefitinib, followed 6-8 weeks later by surgery. An intra-operative radiotherapy boost of 10 Gy was planned. Adjuvant chemotherapy was administrated in ypN1-2 pts. After a median f/u of >10 years, we analyzed Local Control (LC), Metastasis Free Survival (MFS), Disease Free Survival (DFS), Disease Specific Survival (DSS) and Overall Survival (OS). Predictive endpoints of clinical outcomes were tested by univariate and multivariate analysis. Variables analyzed included: age, gefitinib dose and interruptions, adjuvant CT, surgery type, ypT, ypN, and TRG grade. We have also analyzed late toxicity according to CTCAEv4.
Of the 41 initially enrolled pts, 39 were evaluable (27M, 12F). With a median f/u of 133 months, LC, MFS, DFS, OS and DSS at 5 years were 84%; 71%; 64%; 87% and 92%, respectively. The OS and DSS at 10 years were 61,5% and 76%, respectively. Grade 3-4 late toxicity occurred in 38% of pts: sexual (28,2%) and gastrointestinal toxicities (10,2%).
Long term outcomes and late toxicity were similar to previously reported series. The addition of gefitinib did not improve outcomes in LARC. Gefitinib is not recommended for rectal cancer patients who received 5-FU based preoperative CRT. Further studies may identify if gefitinib is beneficial in selected group of patients.
本研究旨在评估吉非替尼联合放化疗（CRT）用于局部晚期直肠癌（LARC）的长期生存情况。
这项先前发表的多中心、开放标签的I-II期研究，纳入LARC患者接受CRT，同时持续静脉输注5-氟尿嘧啶并递增口服吉非替尼剂量，6-8周后进行手术。计划术中放疗增敏10Gy。ypN1-2期患者接受辅助化疗。中位随访超过10年后，我们分析了局部控制（LC）、无转移生存期（MFS）、无病生存期（DFS）、疾病特异性生存期（DSS）和总生存期（OS）。通过单因素和多因素分析测试临床结局的预测终点。分析的变量包括：年龄、吉非替尼剂量和中断情况、辅助化疗、手术类型、ypT、ypN和肿瘤退缩分级（TRG）。我们还根据CTCAEv4分析了晚期毒性。
最初纳入的41例患者中，39例可评估（27例男性，12例女性）。中位随访133个月，5年时的LC、MFS、DFS、OS和DSS分别为84%；71%；64%；87%和92%。10年时的OS和DSS分别为61.5%和76%。38%的患者出现3-4级晚期毒性：性功能障碍（28.2%）和胃肠道毒性（10.2%）。
长期结局和晚期毒性与先前报道的系列相似。添加吉非替尼并未改善LARC的结局。不建议接受基于5-氟尿嘧啶的术前CRT的直肠癌患者使用吉非替尼。进一步研究可能确定吉非替尼是否对特定患者群体有益。
