交替序贯给药可能是克服晚期胰腺导管腺癌 (PDAC) 化疗耐药性的一种有前途的方法。这项研究是一项开放标签、单臂、前瞻性试验，纳入了未经治疗的晚期 PDAC 患者。他们接受了 2 个周期的 NS 方案（白蛋白结合型紫杉醇：125 mg/m2，第 1 天和第 8 天静脉注射，加上 S-1：40-60 mg，每天口服两次，持续 1-14 天），然后接受 2 个周期的 NS 方案GemOx 方案（吉西他滨，第 1 天和第 8 天静脉注射，奥沙利铂：130 mg/m2，第 1 天静脉注射）。主要疗效终点是 6 个月无进展生存率 (PFSR-6m)。次要疗效终点包括总生存期（OS）、无进展生存期（PFS）、客观缓解率（ORR）、疾病控制率（DCR）和不良事件（AE）。使用特定的 mRNA 转录本来探索生存相关基因。42 名患者至少接受了 1 个治疗周期，其中 30 名患者完成了 1 个由 4 个周期组成的交替治疗。 PFSR-6m 为 71% (95% CI = 58%-87%)。中位 PFS 和 OS 分别为 6.53 个月（95% CI = 6.03-8.43）和 11.4 个月（95% CI = 9.8-14.4）。常见的 3-4 级血液学 AE 包括中性粒细胞减少症（30.9%）、白细胞减少症（26.2%）、贫血症（2.4%）和血小板减少症（11.9%）。 OS > 10 个月的患者 HLA-DQA2 高表达，而 OS < 10 个月的患者中黑色素瘤相关抗原基因 (MAGE) 显着上调。NS 和 GemOx 方案交替序贯给药可能是一种新方法。需要进一步研究的晚期 PDAC 患者的一线化疗（ClinicalTrials.gov 标识符：ChiCTR1900024867）。© 作者 2024。由牛津大学出版社出版。

Alternating sequential administration of drugs may be a promising approach to overcome chemotherapy resistance in advanced pancreatic ductal adenocarcinoma (PDAC).This study was an open-label, single-arm, and prospective trial included patients with untreated advanced PDAC. They received 2 cycles of NS regimen (nab-paclitaxel:125 mg/m2, intravenously injected on days 1 and 8, plus S-1:40-60 mg, orally twice per day for 1-14 days) followed by 2 cycles of GemOx regimen (gemcitabine, intravenously injected on days 1 and 8, and oxaliplatin: 130 mg/m2, intravenously injected on day 1). The primary efficacy endpoint was a progression-free survival rate at 6 months (PFSR-6m). The secondary efficacy endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Specific mRNA transcripts were used to explore survival associated genes.Forty-two patients received a minimum of one treatment cycle, and of these, 30 patients completed one alternating treatment consisting of 4 cycles. The PFSR-6m was 71% (95% CI = 58%-87%). The median PFS and OS were 6.53 months (95% CI = 6.03-8.43) and 11.4 months (95% CI = 9.8-14.4), respectively. Common grades 3-4 hematological AEs included neutropenia 30.9%, leukopenia 26.2%, anemia 2.4%, and thrombocytopenia in 11.9%. Patients with OS > 10 months showed high expression of HLA-DQA2 while melanoma-associated antigen genes (MAGE) were notably upregulated in patients with OS < 10 months.The alternating sequential administration of the NS and GemOx regimens may be a novel approach for first-line chemotherapy in patients with advanced PDAC requiring further study (ClinicalTrials.gov Identifier: ChiCTR1900024867).© The Author(s) 2024. Published by Oxford University Press.