A phase II study of neoadjuvant combination chemotherapy with docetaxel, cisplatin, and S-1 for locally advanced resectable gastric cancer: nucleotide excision repair (NER) as potential chemoresistance marker
A phase II study of neoadjuvant combination chemotherapy with docetaxel, cisplatin, and S-1 for locally advanced resectable gastric cancer: nucleotide excision repair (NER) as potential chemoresistance marker
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DOI：
10.1007/s00280-013-2073-5
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发表时间：
2013-03-01
影响因子：
3
通讯作者：
Kato, Junji
中科院分区：
文献类型：
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作者：
Hirakawa, Masahiro;Sato, Yasushi;Kato, Junji
多西紫杉醇、顺铂和 S-1 (DCS) 联合化疗有望成为治疗晚期胃癌的一种有前景的治疗方案。本研究旨在评估新辅助 DCS 化疗治疗局部晚期可切除胃癌的有效性和安全性。局部晚期胃癌患者术前接受 2 个疗程的化疗，第 1-14 天使用 S-1（40 mg/m(2) b.i.d.），第 8 天接受多西他赛（60 mg/m(2)）加顺铂（60 mg/m(2)），每 3 周接受一次标准根治性手术。 4-8周。主要终点是 R0 可切除性。采用免疫组化法检测预处理肿瘤组织中损伤DNA结合蛋白复合物亚基2（DDB2）/切除修复交叉互补1（ERCC1）的表达。共有43例患者接受了新辅助化疗。有效率74.4%，疾病控制率100%。 53.5% 的患者出现 4 级中性粒细胞减少症，16.3% 的患者出现发热性中性粒细胞减少症。非血液学 3/4 级不良事件为厌食 (23.3%)、恶心 (14.0%) 和腹泻 (23.3%)，但这些事件通常是短暂的且可控制。 43例符合条件的患者中，R0切除比例为90.7%，65.9%的患者出现病理缓解。没有与治疗相关的死亡，也没有重大手术并发症。 DDB2和ERCC1表达联合预测化疗耐药的准确率为82.5%。术前DCS联合治疗局部进展期胃癌显示出足够的R0切除率和良好的病理反应，且毒性可控。通过免疫组织化学测定的 DDB2/ERCC1 高表型可能是 DCS 化疗耐药性的有用预测因子。
The combination of docetaxel, cisplatin, and S-1 (DCS) chemotherapy is expected to be a promising regimen for advanced gastric cancer. This study was performed to evaluate the efficacy and safety of neoadjuvant DCS chemotherapy for locally advanced resectable gastric cancer.Patients with locally advanced gastric cancer received 2 courses of preoperative chemotherapy with S-1 (40 mg/m(2) b.i.d.) on days 1-14 and docetaxel (60 mg/m(2)) plus cisplatin (60 mg/m(2)) on day 8 every 3 weeks, followed by standard curative surgery within 4-8 weeks. The primary endpoint was R0 resectability. Expression of damage DNA binding protein complex subunit 2 (DDB2)/excision repair cross-complementing 1 (ERCC1) in the pretreated tumor tissues was examined by immunohistochemistry.A total of 43 patients received neoadjuvant chemotherapy. The response rate was 74.4 %, and disease control ratio was 100 %. Grade 4 neutropenia developed in 53.5 % of patients and febrile neutropenia in 16.3 %. Non-hematological grade 3/4 adverse events were anorexia (23.3 %), nausea (14.0 %), and diarrhea (23.3 %), but these were generally transient and manageable. The proportion of R0 resections in the 43 eligible patients was 90.7 %, and a pathological response was found in 65.9 % of patients. There were no treatment-related deaths and no major surgical complications. The accuracy of the combination of DDB2 and ERCC1 expression for predicting chemoresistance was 82.5 %.Preoperative treatment with DCS combination for locally advanced gastric cancer demonstrated a sufficient R0 resection rate and a good pathological response with manageable toxicities. The DDB2/ERCC1-high phenotype, as determined by immunohistochemistry, may be useful predictor of resistance to DCS chemotherapy.