Yamada Yunami, Fujii Hironori, Watanabe Daichi, Kato-Hayashi Hiroko, Ohata Koichi, Kobayashi Ryo, Ishihara Takuma, Uemura Shinya, Iwashita Takuji, Shimizu Masahito, Suzuki Akio
Department of Pharmacy, Gifu University Hospital, Gifu 501-1194, Japan.
Gifu University Hospital, Innovative and Clinical Research Promotion Center, Gifu University, Gifu 501-1194, Japan.
Cancers (Basel). 2018 Nov 16;10(11):454. doi: 10.3390/cancers10110454.
While modified FOLFIRINOX therapy is effective for treating advanced pancreatic cancer, it frequently causes severe neutropenia. The present study investigated the effect of severe neutropenia on clinical outcomes in advanced pancreatic cancer patients who received modified FOLFIRINOX. The study subjects were 51 patients (30 males and 21 females) with advanced pancreatic cancer who received modified FOLFIRINOX (2h bolus injection of oxaliplatin at 85 mg/m², 2 h bolus injection of L-leucovorin at 200 mg/m², 90min bolus injection of irinotecan at 150 mg/m², followed by continuous infusion of 5-fluorouracil for 46 h at 2400 mg/m² without bolus 5-fluorouracil) during the period from January 2014 to May 2018. No patients had prior history of chemotherapy. Adverse events, including neutropenia, were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. Median overall survival (OS) was the primary endpoint, while median time to treatment failure (TTF), overall response rate (ORR), and the incidence of other adverse events were secondary endpoints. Severe neutropenia (grade ≥3) occurred in 39 patients (76.4%), and Cox proportional hazard analysis identified high total bilirubin level as a significant risk factor. Median duration of OS was significantly longer in patients with severe neutropenia than in those without it (21.3 months versus 8.9 months, = 0.020). Moreover, there was a significant correlation between OS and the grade of neutropenia (r = 0.306, = 0.029). ORR tended to be higher, though not significantly, in patients with severe neutropenia. In contrast, the incidence rates of other adverse events were not different between the two groups. Severe neutropenia is an independent predictor of prognosis in advanced pancreatic cancer patients received modified FOLFIRINOX therapy.
虽然改良的FOLFIRINOX疗法对晚期胰腺癌有效，但它经常导致严重的中性粒细胞减少。本研究调查了严重中性粒细胞减少对接受改良FOLFIRINOX治疗的晚期胰腺癌患者临床结局的影响。研究对象为51例晚期胰腺癌患者（30例男性和21例女性），他们在2014年1月至2018年5月期间接受了改良的FOLFIRINOX治疗（奥沙利铂85mg/m²静脉滴注2小时，亚叶酸钙200mg/m²静脉滴注2小时，伊立替康150mg/m²静脉滴注90分钟，随后在不推注5-氟尿嘧啶的情况下以2400mg/m²持续输注5-氟尿嘧啶46小时）。所有患者均无化疗史。包括中性粒细胞减少在内的不良事件根据《不良事件通用术语标准》第4.0版进行分级。中位总生存期（OS）是主要终点，而中位治疗失败时间（TTF）、总缓解率（ORR）和其他不良事件的发生率是次要终点。39例患者（76.4%）发生了严重中性粒细胞减少（≥3级），Cox比例风险分析确定高总胆红素水平是一个显著的危险因素。严重中性粒细胞减少患者的中位OS持续时间显著长于无严重中性粒细胞减少的患者（21.3个月对8.9个月，P = 0.020）。此外，OS与中性粒细胞减少分级之间存在显著相关性（r = 0.306，P = 0.029）。严重中性粒细胞减少患者的ORR虽无显著差异，但有升高趋势。相比之下，两组其他不良事件的发生率没有差异。严重中性粒细胞减少是接受改良FOLFIRINOX治疗的晚期胰腺癌患者预后的独立预测因素。
