Gastroenterology Center, Japanese Foundation for Cancer Research, Cancer Institute Hospital, Tokyo, Japan.
Cancer Center, Gifu University Hospital, Gifu, Japan.
PLoS One. 2021 Feb 8;16(2):e0246160. doi: 10.1371/journal.pone.0246160. eCollection 2021.
The objectives were to describe treatment sequences for advanced colorectal cancer (CRC), use of second-line FOLFIRI (leucovorin, 5-fluorouracil, irinotecan) plus antiangiogenic drug (bevacizumab, ramucirumab, aflibercept beta) therapy, and the factors associated with the duration of antitumor drug treatment from second-line antiangiogenic therapy in Japan. This retrospective observational study was conducted using a Japanese hospital-based administrative database. Patients were enrolled if they started adjuvant therapy (and presumably experienced early recurrence) or first-line treatment for advanced CRC between May 2016 and July 2019, and were analysed until September 2019. Factors associated with overall treatment duration from second-line treatment with FOLFIRI plus antiangiogenic drugs were explored with multivariate Cox regression analysis. The most common first-line treatments were FOLFOX (leucovorin, 5-fluorouracil, oxaliplatin) or CAPOX (capecitabine, oxaliplatin) with bevacizumab (presumed RAS-mutant CRC) and FOLFOX with panitumumab (presumed RAS-wild type CRC). The most common second-line treatments were FOLFIRI-based. Many patients did not transition to subsequent lines of therapy. For second-line treatment, antiangiogenic drugs were prescribed more often for patients with presumed RAS-mutant CRC, right-sided CRC, and independent activities of daily living (ADL). The median duration of second-line FOLFIRI plus antiangiogenic drug treatment was 4.5 months; 66.2% of patients transitioned to third-line therapy. Low body mass index and not fully independent ADL were significantly associated with shorter overall duration of antitumor drug treatment from second-line therapy. Left-sided CRC, presumed RAS-wild type CRC, previous use of oral fluoropyrimidines and use of proteinuria qualitative tests, antihypertensives, or anticholinergics during second-line therapy were significantly associated with longer treatment. Treatment of advanced CRC in Japan is consistent with both international and Japanese guidelines, but transition rates to subsequent therapies need improvement. In addition to antitumor drug treatment, better ADL, higher body mass index, management of hypertension, and proteinuria tests were associated with continuation of sequential therapy that included antiangiogenic drugs.
目的在于描述晚期结直肠癌(CRC)的治疗顺序,使用二线 FOLFIRI(亚叶酸钙、5-氟尿嘧啶、伊立替康)加抗血管生成药物(贝伐珠单抗、雷莫芦单抗、阿柏西普)治疗,并探讨日本二线抗血管生成治疗中与抗肿瘤药物治疗持续时间相关的因素。本回顾性观察性研究使用了日本医院的管理数据库。如果患者在 2016 年 5 月至 2019 年 7 月期间开始辅助治疗(推测为早期复发)或一线治疗晚期 CRC,则纳入本研究,并分析至 2019 年 9 月。采用多变量 Cox 回归分析探讨与二线 FOLFIRI 联合抗血管生成药物治疗总持续时间相关的因素。最常见的一线治疗是 FOLFOX(亚叶酸钙、5-氟尿嘧啶、奥沙利铂)或 CAPOX(卡培他滨、奥沙利铂)联合贝伐珠单抗(推测为 RAS 突变型 CRC)和 FOLFOX 联合帕尼单抗(推测为 RAS 野生型 CRC)。最常见的二线治疗是基于 FOLFIRI 的治疗。许多患者未转至后续治疗线。对于二线治疗,抗血管生成药物更常用于推测为 RAS 突变型 CRC、右侧 CRC 和独立日常生活活动(ADL)的患者。二线 FOLFIRI 联合抗血管生成药物治疗的中位持续时间为 4.5 个月;66.2%的患者转至三线治疗。低体重指数和不完全独立的 ADL 与二线治疗的抗肿瘤药物总持续时间较短显著相关。左侧 CRC、推测为 RAS 野生型 CRC、二线治疗期间曾使用口服氟嘧啶和蛋白尿定性检测、降压药或抗胆碱能药物与治疗时间延长显著相关。日本晚期 CRC 的治疗与国际和日本指南一致,但向后续治疗的转化率有待提高。除抗肿瘤药物治疗外,更好的 ADL、更高的体重指数、高血压管理和蛋白尿检测与包括抗血管生成药物在内的序贯治疗的持续相关。