Division of Hematology & Oncology, George Washington University, Washington, DC, USA.
Ipsen, Cambridge, MA, USA.
Curr Med Res Opin. 2022 Aug;38(8):1295-1303. doi: 10.1080/03007995.2022.2059976. Epub 2022 Apr 22.
Chemotherapy-related adverse events (AEs) can negatively impact the care of patients. The prevention and management of AEs often require additional medications. This study evaluated the percentages of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) undergoing second-line therapy with 5-fluorouracil (5-FU)-based regimens that experienced AEs during treatment and received medication to manage those AEs.
We conducted a retrospective observational analysis utilizing the Flatiron Health database of adult patients with mPDAC who started second-line therapy between January 2016 and August 2020. The occurrence of diarrhea, fatigue, nausea and vomiting, neuropathy, and hematologic AEs including G3/G4 anemia, neutropenia, and thrombocytopenia was assessed. The use of concomitant medications including atropine and granulocyte colony stimulating factor (G-CSF) was assessed.
Of the 825 eligible patients, 29.0% ( = 239) received FOLFIRINOX, 24.0% ( = 198) received FOLFOX, 6.8% ( = 56) received FOLFIRI, and 40.2% ( = 332) received liposomal irinotecan-based regimens. FOLFIRI and FOLFIRINOX regimens were associated with the highest rates of anemia (16.1% and 15.5%), neutropenia (19.6% and 22.6%), and thrombocytopenia (14.3% and 9.6%). The liposomal irinotecan and FOLFOX regimens were associated with lower rates of anemia (11.8% and 12.1%), neutropenia (12.4% and 14.7%), and thrombocytopenia (2.4% and 8.1%). G-CSF use was observed among 63.6%, 34.9%, 33.9%, and 44.9% of patients treated with FOLFIRINOX, FOLFOX, FOLFIRI, and liposomal irinotecan-based regimens, respectively. Diarrhea was observed among 12.5%, 4.5%, 12.5%, and 10.2% of patients who were treated with FOLFIRINOX, FOLFOX, FOLFIRI, and liposomal irinotecan-based regimens, respectively. Nausea and vomiting occurred in 14.9%, 12.6%, 10.5%, and 13.1% of patients treated with FOLFIRINOX, FOLFOX, FOLFIRI, and liposomal irinotecan-based regimens, respectively. Atropine use was higher in patients treated with FOLFIRINOX and FOLFIRI (90.8% and 94.6%, respectively) than in patients treated with liposomal irinotecan-based regimens (75.6%).
In patients with mPDAC who received second-line therapy, those who received liposomal irinotecan-based regimens had the lowest rates of anemia, neutropenia, and thrombocytopenia compared to FOLFIRI, FOLFIRINOX, and FOLFOX, while requiring a similar or lower level of medication to treat and manage those adverse events. Patients treated with FOLFIRI received the highest dose of pegfilgrastim to manage neutropenia. The results of this real-world analysis are consistent with prior evaluations of patients with mPDAC and highlight the importance of managing adverse events and associated cost implications.
化疗相关不良反应（AE）可能会对患者的治疗产生负面影响。AE 的预防和管理通常需要额外的药物。本研究评估了转移性胰腺导管腺癌（mPDAC）患者二线接受 5-氟尿嘧啶（5-FU）为基础的方案治疗时出现 AE 并接受药物治疗以管理这些 AE 的比例。
我们利用 Flatiron Health 数据库，对 2016 年 1 月至 2020 年 8 月间二线接受治疗的 mPDAC 成年患者进行了回顾性观察性分析。评估了腹泻、疲劳、恶心和呕吐、神经病变以及包括 G3/G4 贫血、中性粒细胞减少和血小板减少在内的血液学 AE 的发生情况。评估了同时使用包括阿托品和粒细胞集落刺激因子（G-CSF）在内的药物的情况。
在 825 名符合条件的患者中，29.0%（239 名）接受了 FOLFIRINOX 治疗，24.0%（198 名）接受了 FOLFOX 治疗，6.8%（56 名）接受了 FOLFIRI 治疗，40.2%（332 名）接受了脂质体伊立替康为基础的方案治疗。FOLFIRI 和 FOLFIRINOX 方案与最高的贫血（16.1%和 15.5%）、中性粒细胞减少（19.6%和 22.6%）和血小板减少（14.3%和 9.6%）发生率相关。脂质体伊立替康和 FOLFOX 方案与较低的贫血（11.8%和 12.1%）、中性粒细胞减少（12.4%和 14.7%）和血小板减少（2.4%和 8.1%）发生率相关。分别有 63.6%、34.9%、33.9%和 44.9%接受 FOLFIRINOX、FOLFOX、FOLFIRI 和脂质体伊立替康为基础的方案治疗的患者使用了 G-CSF。接受 FOLFIRINOX、FOLFOX、FOLFIRI 和脂质体伊立替康为基础的方案治疗的患者中分别有 12.5%、4.5%、12.5%和 10.2%发生了腹泻。接受 FOLFIRINOX、FOLFOX、FOLFIRI 和脂质体伊立替康为基础的方案治疗的患者中分别有 14.9%、12.6%、10.5%和 13.1%发生了恶心和呕吐。接受 FOLFIRINOX 和 FOLFIRI（分别为 90.8%和 94.6%）治疗的患者比接受脂质体伊立替康为基础的方案治疗的患者（75.6%）更常使用阿托品。
在接受二线治疗的 mPDAC 患者中，与 FOLFIRI、FOLFIRINOX 和 FOLFOX 相比，接受脂质体伊立替康为基础的方案治疗的患者贫血、中性粒细胞减少和血小板减少的发生率最低，而需要类似或更低水平的药物来治疗和管理这些 AE。接受 FOLFIRI 治疗的患者接受了最高剂量的培非格司亭来治疗中性粒细胞减少症。本真实世界分析的结果与先前对 mPDAC 患者的评估一致，并强调了管理 AE 及其相关成本影响的重要性。
