Background

Although FOLFIRINOX is currently one of the standard therapies for chemotherapy-naïve patients with metastatic pancreatic cancer (MPC), the high rate of febrile neutropenia (FN) presents a clinical problem. This study aimed to evaluate the safety and efficacy of primary prophylactic pegfilgrastim with FOLFIRINOX in Japanese MPC patients.

Methods

FOLFIRINOX (intravenous oxaliplatin 85 mg/m², irinotecan 180 mg/m², levofolinate 200 mg/m², 5-fluorouracil (5-FU) bolus 400 mg/m² and 5-FU 46 h infusion 2400 mg/m²) and pegfilgrastim 3.6 mg on day 4 or 5, every 2 weeks was administered to previously untreated MPC patients. The primary endpoint was the incidence of FN during the first 3 cycles. The planned sample size was 35 patients, but the trial was predefined to discontinue enrollment for safety if 4 patients developed FN.

Results

At the enrollment of 22 patients, 4 patients developed FN in the first cycle, resulting in an incidence of FN of 18% {95% confidence interval [CI], 0.5–40.3%}, and enrollment was discontinued early. The incidence of grade 3 or higher neutropenia was 36.4%. Median relative dose intensities during the initial 3 cycles of oxaliplatin, irinotecan, bolus 5-FU, infusional 5-FU, and levofolinate maintained high (100%, 89.0%, 100%, 66.0%, and 100%, respectively). Response rate and median overall survival were 54.5% (95% CI 32.7–74.9) and 15.7 months (95% CI 7.9–18.8), respectively.

Conclusions

This phase II study could not demonstrate any reduction in the incidence of FN, nevertheless some patients experience benefits for efficacy by maintaining dose intensity using prophylactic pegfilgrastim.

Trial registration

http://www.umin.ac.jp/ctr/index-j.htm, UMIN000017538. Date of registration: May/13/2015

中文翻译：

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FOLFIRINOX 与初级预防性培非格司亭治疗未接受化疗的日本转移性胰腺癌患者的 II 期研究

背景

尽管 FOLFIRINOX 目前是未接受化疗的转移性胰腺癌 (MPC) 患者的标准疗法之一，但发热性中性粒细胞减少症 (FN) 的高发生率是一个临床问题。本研究旨在评估初级预防性培非格司亭与 FOLFIRINOX 在日本 MPC 患者中的安全性和有效性。

方法

FOLFIRINOX（静脉奥沙利铂 85 mg/m ²，伊立替康 180 mg/m ²，左叶叶酸 200 mg/m ²，5-氟尿嘧啶 (5-FU) 推注 400 mg/m ²和 5-FU 46 小时输注 2400 mg/m ² ) 和 pegfilgrastim 3.6 mg 在第 4 天或第 5 天，每 2 周给予先前未治疗的 MPC 患者。主要终点是前 3 个周期内 FN 的发生率。计划的样本量为 35 名患者，但如果 4 名患者出现 FN，该试验预定义为停止入组以确保安全。

结果

在 22 名患者入组时，4 名患者在第一个周期出现 FN，导致 FN 的发生率为 18% {95% 置信区间 [CI]，0.5-40.3%}，并且提前终止了入组。3 级或更高级别中性粒细胞减少症的发生率为 36.4%。在奥沙利铂、伊立替康、推注 5-FU、输注 5-FU 和左叶叶酸的最初 3 个周期中，中位相对剂量强度保持较高（分别为 100%、89.0%、100%、66.0% 和 100%）。缓解率和中位总生存期分别为 54.5% (95% CI 32.7–74.9) 和 15.7 个月 (95% CI 7.9–18.8)。

结论

这项 II 期研究无法证明 FN 的发生率有任何降低，但一些患者通过使用预防性 pegfilgrastim 维持剂量强度而体验到疗效益处。

试用注册

http://www.umin.ac.jp/ctr/index-j.htm，UMIN000017538。注册日期：2015 年 5 月/13 日