基于奥沙利铂的化疗在晚期神经内分泌肿瘤中的应用：临床结果及与生物学因素的初步相关性

Oxaliplatin-Based Chemotherapy in Advanced Neuroendocrine Tumors: Clinical Outcomes and Preliminary Correlation with Biological Factors.

作者信息

Spada Francesca, Antonuzzo Lorenzo, Marconcini Riccardo, Radice Davide, Antonuzzo Andrea, Ricci Sergio, Di Costanzo Francesco, Fontana Annalisa, Gelsomino Fabio, Luppi Gabriele, Nobili Elisabetta, Galdy Salvatore, Cella Chiara Alessandra, Sonzogni Angelica, Pisa Eleonora, Barberis Massimo, Fazio Nicola

机构信息

Gastrointestinal Medical Oncology and Neuroendocrine Tumors Unit, European Institute of Oncology, Milan, Italy.

出版信息

Neuroendocrinology. 2016;103(6):806-14. doi: 10.1159/000444087. Epub 2016 Jan 21.

DOI:10.1159/000444087

PMID:26789262

Abstract

PURPOSE

The role of chemotherapy in low-/intermediate-grade neuroendocrine tumors (NETs) is still debated. We present the results of an Italian multicenter retrospective study evaluating activity and toxicity of oxaliplatin-based chemotherapy in patients with advanced NETs.

METHODS

Clinical records from 5 referral centers were reviewed. Disease control rate (DCR) corresponding to PR + SD (partial response + stable disease) at 6 months, progression-free survival (PFS), overall survival (OS) and toxicity were calculated. Ki67 labeling index, grade of differentiation and excision- repair-cross-complementing group 1 (ERCC-1) were analyzed in tissue tumor samples.

RESULTS

Seventy-eight patients entered the study. Primary sites were: pancreas in 46, gastrointestinal in 24, lung in 19 and unknown in 10% of patients. The vast majority were G2 (2010 WHO classification). Eighty-six percent of the patients were metastatic, and 87% were pretreated and progressive to previous therapies. Sixty-five percent of the patients received capecitabine/oxaliplatin (CAPOX), 6% gemcitabine/oxaliplatin (GEMOX), and 29% leucovorin/fluorouracil/oxaliplatin (FOLFOX-6). PR occurred in 26% of the patients, half of them with pancreatic NETs, and SD in 54%. With a median follow-up of 21 months, the median PFS and OS were 8 and 32 months with 70 and 45 events, respectively. The most frequent G3 toxicities were neurological and gastrointestinal. ERCC-1 immunohistochemical overexpression was positive in 4/28 evaluated samples, with no significant correlation with clinical outcome.

CONCLUSION

This analysis suggests that oxaliplatin-based chemotherapy can be active with a manageable safety profile in advanced NETs irrespective of the primary sites and tumor grade. The 80% DCR and 8-month PFS could justify a prospective study in NETs with intermediate biological characteristics, especially with pancreatic primary tumors.

摘要

目的

化疗在低/中级神经内分泌肿瘤（NETs）中的作用仍存在争议。我们展示了一项意大利多中心回顾性研究的结果，该研究评估了以奥沙利铂为基础的化疗在晚期NETs患者中的活性和毒性。

方法

回顾了5个转诊中心的临床记录。计算了6个月时对应PR + SD（部分缓解 + 疾病稳定）的疾病控制率（DCR）、无进展生存期（PFS）、总生存期（OS）和毒性。在组织肿瘤样本中分析了Ki67标记指数、分化程度和切除修复交叉互补组1（ERCC-1）。

结果

78名患者进入研究。原发部位为：胰腺46例，胃肠道24例，肺19例，10%的患者原发部位不明。绝大多数为G2（2010年WHO分类）。86%的患者有转移，87%的患者接受过预处理且对先前治疗进展。65%的患者接受了卡培他滨/奥沙利铂（CAPOX），6%的患者接受了吉西他滨/奥沙利铂（GEMOX），29%的患者接受了亚叶酸钙/氟尿嘧啶/奥沙利铂（FOLFOX-6）。26%的患者出现PR，其中一半为胰腺NETs患者，54%的患者疾病稳定。中位随访21个月，中位PFS和OS分别为8个月和32个月，分别有70例和45例事件。最常见的3级毒性为神经和胃肠道毒性。4/28例评估样本中ERCC-1免疫组化过表达呈阳性，与临床结果无显著相关性。