Hagiwara Yuya, Nakasya Akio, Matsumoto Toshihiko, Ikoma Tatsuki, Yamamoto Yoshiyuki, Kurioka Yusuke, Tsuduki Takao, Kajiwara Takeshi, Nishina Tomohiro, Yamashita Natsumi, Moriwaki Toshikazu, Hyodo Ichinosuke
Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Ehime, Japan.
J Gastrointest Oncol. 2022 Dec;13(6):2769-2778. doi: 10.21037/jgo-22-499.
Paclitaxel or nanoparticle albumin-bound paclitaxel combined with ramucirumab (PTX/nab-PTX + RAM) is widely used as second-line chemotherapy for advanced gastric cancer (AGC), but severe neutropenia often develops with this regimen. Although previous studies have reported that severe neutropenia is a favorable prognostic factor in cancer chemotherapy, it is unclear in AGC patients receiving PTX/nab-PTX + RAM. In addition, the risk factors for early-onset of severe neutropenia (EOSN) still remain unknown.
Among patients with AGC treated with PTX/nab-PTX (on day 1, 8, and 15) + RAM (on day 1 and 15) every 4 weeks as second-line therapy from January 2017 to June 2020, those with grade 0 or 1 neutropenia before the treatment were retrospectively studied. Blood tests were performed on the day of treatment each time, and disease progression was primarily determined by computed tomography every 8±2 weeks. EOSN was defined as grade 4 neutropenia that occurred during the first 28 days. The risk factors for EOSN were investigated using multivariate logistic regression analysis. Progression-free survival (PFS) and overall survival (OS) in patients with and without EOSN were investigated using multivariate analysis with a Cox proportional hazards model.
The clinical data of 244 patients were analyzed. EOSN was observed in 51 (20.9%) patients. Multivariate analysis identified the following five risk factors for EOSN: age ≥65 years [odds ratio (OR), 2.75], presence of primary tumor (OR, 2.82), presence of peritoneal metastasis (OR, 2.52), grade 1 neutropenia (OR, 3.32), and high serum level of alkaline phosphatase (OR, 2.34). The PFS was significantly longer in patients with EOSN than in those without EOSN [adjusted hazard ratio (HR), 0.61; 95% CI, 0.41-0.92] and the OS tended to be longer in patients with EOSN than in those without EOSN (adjusted HR, 0.73; 95% CI, 0.47-1.12). HR was adjusted with patient background factors and blood test data considered important as predictive or prognostic factors.
EOSN may be associated with favorable outcomes in patients with AGC treated with PTX/nab-PTX + RAM. We should carefully try to treat them keeping the risk factors in mind.
紫杉醇或纳米白蛋白结合型紫杉醇联合雷莫西尤单抗（PTX/纳米白蛋白结合型紫杉醇+雷莫西尤单抗）被广泛用作晚期胃癌（AGC）的二线化疗方案，但该方案常导致严重中性粒细胞减少。尽管既往研究报道严重中性粒细胞减少是癌症化疗中的一个有利预后因素，但在接受PTX/纳米白蛋白结合型紫杉醇+雷莫西尤单抗治疗的AGC患者中尚不清楚。此外，严重中性粒细胞减少早期发作（EOSN）的危险因素仍不明确。
回顾性研究2017年1月至2020年6月期间接受PTX/纳米白蛋白结合型紫杉醇（第1、8和15天）+雷莫西尤单抗（第1和15天）每4周作为二线治疗的AGC患者中，治疗前中性粒细胞减少为0级或1级的患者。每次治疗当天进行血液检查，疾病进展主要通过每8±2周的计算机断层扫描确定。EOSN定义为治疗开始后28天内发生的4级中性粒细胞减少。采用多因素logistic回归分析研究EOSN的危险因素。采用Cox比例风险模型进行多因素分析，研究有无EOSN患者的无进展生存期（PFS）和总生存期（OS）。
分析了244例患者的临床资料。51例（20.9%）患者出现EOSN。多因素分析确定了EOSN的以下五个危险因素：年龄≥65岁[比值比（OR），2.75]、存在原发性肿瘤（OR，2.82）、存在腹膜转移（OR，2.52）、1级中性粒细胞减少（OR，3.32）和血清碱性磷酸酶水平高（OR，2.34）。有EOSN的患者PFS显著长于无EOSN的患者[校正风险比（HR），0.61；95%可信区间（CI），0.41-0.92]，有EOSN的患者OS有长于无EOSN患者的趋势（校正HR，0.73；95%CI，0.47-1.12）。HR经患者背景因素和作为预测或预后因素被认为重要的血液检查数据校正。
在接受PTX/纳米白蛋白结合型紫杉醇+雷莫西尤单抗治疗的AGC患者中，EOSN可能与良好预后相关。我们应牢记危险因素，谨慎地对他们进行治疗。
