Yoshida Yoichiro, Sakamoto Ryohei, Kajitani Ryuji, Munechika Taro, Matsumoto Yoshiko, Komono Akira, Aisu Naoya, Daibo Kojima, Kiyomi Fumihiko, Hasegawa Suguru
Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine, Fukuoka, Japan
Department of Gastroenterological Surgery, Fukuoka University Faculty of Medicine, Fukuoka, Japan.
Anticancer Res. 2018 Jul;38(7):4367-4373. doi: 10.21873/anticanres.12738.
BACKGROUND/AIM: TAS-102 has led to a significant improvement in overall survival (OS) and progression-free survival (PFS) of patients with metastatic colorectal cancer (mCRC). Neutropenia is the most common adverse event and an important factor impacting chemotherapy continuation. In this retrospective study, factors associated with grade ≥3 neutropenia, that is frequently observed in TAS-102-treated patients, were examined.
The medical records of 41 patients with CRC who received TAS-102 between October 2014 and June 2017 at the Fukuoka University Hospital were retrospectively reviewed. Response rate, PFS, OS, and adverse events were analyzed using KRAS mutation, administration method, concomitant drug administration, neutrophil-to-lymphocyte ratio (NLR), and Onodera's prognostic nutritional index (Onodera's index) as a stratification factors.
Both PFS and OS were significantly higher with TAS-102 plus bevacizumab combination therapy. Biweekly administration (7.1%) was associated with significantly less neutropenia compared to normal administration (44.4%). DCR with biweekly administration was better than that with normal administration, although without statistical significance. No significant difference was observed in OS rates between the biweekly and normal administration regimens; however, the biweekly regimen was associated with significantly prolonged PFS. By multivariate analysis, a significant difference was noted in the Onodera's index for OS and in the administration method and NLR for PFS.
Biweekly administration without a change in the drug dose intensity was associated with reduced neutropenia in patients with mCRC. The effects and adverse events of TAS-102 were associated with concomitant drug administration, administration method, and nutritional status.
背景/目的：TAS-102已使转移性结直肠癌（mCRC）患者的总生存期（OS）和无进展生存期（PFS）得到显著改善。中性粒细胞减少是最常见的不良事件，也是影响化疗持续进行的重要因素。在这项回顾性研究中，对TAS-102治疗患者中经常观察到的≥3级中性粒细胞减少相关因素进行了研究。
回顾性分析了2014年10月至2017年6月在福冈大学医院接受TAS-102治疗的41例CRC患者的病历。以KRAS突变、给药方式、联合用药、中性粒细胞与淋巴细胞比值（NLR）和小野寺预后营养指数（小野寺指数）作为分层因素，分析缓解率、PFS、OS和不良事件。
TAS-102联合贝伐单抗治疗的PFS和OS均显著更高。与常规给药（44.4%）相比，两周一次给药（7.1%）的中性粒细胞减少明显更少。两周一次给药的疾病控制率（DCR）优于常规给药，尽管无统计学意义。两周一次和常规给药方案的OS率无显著差异；然而，两周一次给药方案的PFS显著延长。多因素分析显示，小野寺指数对OS有显著差异，给药方式和NLR对PFS有显著差异。
在不改变药物剂量强度的情况下，两周一次给药可降低mCRC患者的中性粒细胞减少。TAS-102的疗效和不良事件与联合用药、给药方式和营养状况有关。
