白蛋白结合型紫杉醇用于HER2阴性晚期胃癌一线化疗中的疗效分析

Albumin-bound paclitaxel in first-line chemotherapy for patients with HER2-negative advanced gastric cancer

  • 摘要: 目的 评估纳米白蛋白结合型紫杉醇(nab-PTX)联合化疗一线治疗HER2阴性的不可切除或复发晚期胃癌患者的有效性和安全性,评价临床特性与患者生存期的相关性。方法 选取2011年12月17日-2018年1月10日,本研究入组的44例HER2阴性的晚期胃癌患者,包括34例男性、10例女性,中位年龄57(28~85)岁。其中19例(38.6%)接受了胃造瘘术。组织学类型中分化17例,低分化27例。转移部位肝15例、肺4例、淋巴结19例、骨3例、腹膜6例。以上患者均接受白蛋白结合型紫杉醇联合疗法作为一线治疗。观察患者无进展生存期(progression free survival,PFS)、总生存期(overall survival,OS)、临床特征、客观缓解率(objective response rate,ORR)、疾病控制率(disease control rate,DCR)和治疗相关不良反应。结果 治疗周期中位数为4(范围:2~8)。ORR为40.9%,DCR为90.9%。中位PFS为5.1个月(95% CI:3.9~6.3),OS为14.1个月(95% CI:10.7~14.5)。3级/4级毒性反应发生率为15.9%。最常见的3级不良事件为白细胞减少症(chemotherapy-induced leukopenia,CIL)(n=7,15.9%)。1级和2级非血液学毒性反应包括恶心和呕吐(n=16,36.3%)以及手足综合征(n=10,22.7%)、厌食症(n=10,22.7%)、疲乏(n=9,20.4%)、脱发(n=9,20.4%)、外周感觉神经病变(n=6,13.6%)。多因素分析显示中位CEA<5μg/L是OS延长的重要预测因子(HR=3.5,95% CI:1.48~8.23,P=0.004)。与化疗诱发的3级和4级CIL患者相比,发生0~2级CIL患者的PFS和OS有改善的趋势(HR=2.734,95% CI:1.00~7.46,P=0.050;HR=17.79,95% CI:4.7~66.4,P=0.000)。Nab-PTX联合替吉奥胶囊与Nab-PTX联合顺铂的OS有统计学差异(12.5个月 vs 17.0个月;HR=0.513,95% CI:0.31~0.84,P=0.005)。早发CIL患者的OS为18.2个月,晚发CIL患者的OS为11.5个月(HR=2.48,95% CI:1.13~5.42,P=0.02)。结论 白蛋白结合型紫杉醇联合替吉奥胶囊或联合顺铂可作为HER2阴性的晚期胃癌患者的一线治疗方案。化疗诱发的0~2级CIL和早发CIL的患者预后较好。可根据中位CEA<5μg/L的标准来选择合适的胃癌患者,以提高nab-PTX治疗胃癌的效果。

     

    Abstract: Objective To evaluate the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel)-combined chemotherapy (CT) as first-line for patients with her-2 negative advanced gastric cancer (GC) in Chinese single-center practice and explore the correlation between clinical characteristics and survival. Methods From December 17,2011 to January 10,2018,44 patients who underwent nab-paclitaxel (nab-PTX) combined therapy as first line with HER2-negative advanced GC were included in this study,including 34 males and 10 females with median age of 57 years (28-85 years).Of the 44 cases,19 (38.6%) cases underwent percutaneous endoscopic gastrostomy.Moderate differentiation was found in 17 cases and poor differentiation in 27 cases.Liver metastasis was found in 15 cases,lung metastasis in 4 cases,lymph node metastasis in 19 cases,bone metastasis in 3 cases and peritoneal metastasis in 6 cases.All cases had undergone nanoparticle albumin-bound paclitaxel (nab-paclitaxel)-combined chemotherapy (CT) as first-line.The progression free survival (PFS),overall survival (OS),clinical characteristics,objective response rate (ORR),disease control rate (DCR) and treatment-related adverse efects (AEs) were reviewed and evaluated. Results The median number of cycles was 4 (range:2-8).Their overall response rate (ORR) was 40.9% and the disease control rate (DCR) was 90.9%.Median progression-free survival (PFS) and overall survival (OS) were 5.1 months (95% CI:3.9-6.3 months) and 14.1 months (95% CI:10.7-14.5 months),respectively.The toxicities associated with nab-PTX combined therapy were generally tolerable with a total grade 3/4 AEs rate of 15.9%.The most common grade 3 adverse events were leukopenia (n=7,15.9%).Grade 1-2 non-hematologic toxicities included nausea and vomiting (n=16,36.3%),hand–foot syndrome (n=10,22.7%),anorexia (n=10,22.7%),fatigue (n=9,20.4%),alopecia (n=9,20.4%),and peripheral sensory neuropathy (n=6,13.6%).According to multivariate analysis,median CEA<5μg/L was a significant predictor for longer OS (HR,3.5;95% CI,1.48-8.23,P=0.004).Patients with G0-2 chemotherapy-induced leukopenia (CIL) showed an improved trend in PFS (HR,2.734,95% CI,1.00-7.46,P=0.05) and OS (HR,17.79;95% CI,4.7-66.4,P=0.000) when compared with those with G3-4 CIL.The OS of patients treated with nab-PTX combined S1 versus Cisplatin were significant different (12.5 months vs 17.0 months;HR:0.513;95% CI,0.31-0.84;P=0.005).The OS of patients with early onset of CIL were 18.2 months compared with 11.5 months in those of later onset of CIL (HR,2.48;95% CI,1.13-5.42,P=0.02). Conclusion Nab-paclitaxel (nab-PTX) combined S1 or Cisplatin may be options as first line for patients with HER-2 negative advanced gastric cancer.Patients who experienced G0-2 chemotherapy-induced leukopenia (CIL) and early-onset CIL have more favorable prognosis.Patients with CEA<5μg/L will be more likely to achieve improvement from nab-PTX therapy.

     

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