Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.
Liver Int. 2020 Oct;40(10):2535-2543. doi: 10.1111/liv.14538. Epub 2020 Jun 9.
BACKGROUND & AIMS: Gemcitabine plus cisplatin (GC) remains the standard, frontline therapy for advanced biliary tract cancer (ABTC). The JCOG1113 study suggested that gemcitabine plus S-1 (GS) had noninferior median overall survival and comparable incidence of significant neutropenia as compared to GC treatments. This study evaluates the efficacy and safety of a modified GS regimen.
The eligible patients with chemonaive, measurable ABTC received 800 mg/m of gemcitabine on day 1 and 80 mg/m /day of S-1 (80/100/120 mg for patients with body surface <1.25/ ≥1.25 and <1.5/ ≥1.5 m respectively). The primary endpoint was the 12-week disease control rate (12-week DCR: objective response and stable disease ≥ 12 weeks). Per the p0 = 40% and p1 = 60% (α/β = 0.05/0.2) assumption, Simon's optimal two-stage design indicated 12-week DCR in ≥ 24 of 46 evaluable patients for significant activity. Tumour responses were assessed every 6 weeks.
Fifty-one patients were enrolled and most of them had intrahepatic cholangiocarcinoma (64.7%), metastatic disease (84.3%) and disease-related symptoms (82.4%). On intention-to-treat analysis, 11 (21.6%) patients showed partial response, whereas 21 (41.2%) showed stable disease ≥ 12 weeks. The progression-free and overall survival were 5.4 months (95% confidence interval [CI]: 3.5-7.0), and 12.7 months (95% CI: 6.1-15.6) respectively. The study met its primary endpoint with a 12-week DCR of 69.6% in 46 evaluable patients. Grade 3/4 treatment-related adverse eventsoccurred in < 6% of patients of all individual items. The mean dose intensities of S-1 and gemcitabine were 87.1% and 92.5% respectively.
Modified GS showed moderate efficacy with a favourable safety profile in ABTC patients, thus mandating further assessment. ClinicalTrials.gov number: NCT02425137.
吉西他滨联合顺铂（GC）仍然是晚期胆道癌（ABTC）的标准一线治疗方法。JCOG1113 研究表明，吉西他滨联合 S-1（GS）在中位总生存期和严重中性粒细胞减少症的发生率方面与 GC 治疗无差异。本研究评估了改良 GS 方案的疗效和安全性。
符合条件的初治、可测量的 ABTC 患者接受吉西他滨 800 mg/m2 于第 1 天，S-1 80 mg/m2/天（对于体表面积＜1.25/≥1.25 和＜1.5/≥1.5 m 的患者分别为 80/100/120 mg）。主要终点为 12 周疾病控制率（12 周 DCR：客观缓解和稳定疾病≥12 周）。根据 p0 = 40%和 p1 = 60%（α/β = 0.05/0.2）假设，Simon 的最优两阶段设计表明，46 例可评估患者中≥24 例患者的 12 周 DCR 有显著活性。每 6 周评估肿瘤反应。
51 例患者入组，其中大多数为肝内胆管癌（64.7%）、转移性疾病（84.3%）和与疾病相关的症状（82.4%）。意向治疗分析显示，11 例（21.6%）患者出现部分缓解，21 例（41.2%）患者稳定疾病≥12 周。无进展生存期和总生存期分别为 5.4 个月（95%置信区间：3.5-7.0）和 12.7 个月（95%置信区间：6.1-15.6）。该研究达到了主要终点，46 例可评估患者的 12 周 DCR 为 69.6%。所有单个项目中，3/4 级治疗相关不良事件发生率＜6%。S-1 和吉西他滨的平均剂量强度分别为 87.1%和 92.5%。
改良 GS 在 ABTC 患者中显示出中等疗效和良好的安全性，因此需要进一步评估。临床试验注册号：NCT02425137。
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