Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.
Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
Oncologist. 2020 Dec;25(12):e1921-e1929. doi: 10.1002/onco.13550. Epub 2020 Oct 31.
The combination of ramucirumab (8 mg/kg intravenous, day 1 every 2 weeks) and FOLFOX4 as first-line treatment in patients with advanced hepatocellular carcinoma (HCC) was not sufficiently tolerated. Preliminary efficacy data suggest that the combination may provide clinical benefit to patients with HCC. Dose modification and patient selection should be considered for the future development of ramucirumab plus FOLFOX chemotherapy for advanced HCC.
The objective of this study was to investigate the safety, preliminary efficacy, pharmacokinetics, and immunogenicity of ramucirumab plus FOLFOX4 as first-line treatment in patients with advanced hepatocellular carcinoma (HCC).
Patients received ramucirumab (8 mg/kg) intravenously (IV) on day 1, followed by FOLFOX4 (oxaliplatin 85 mg/m IV on day 1, folinic acid 200 mg/m IV, bolus fluorouracil [5-FU] 400 mg/m , and a continuous infusion of 5-FU 600 mg/m over 22 hours, on days 1 and 2) every 2 weeks. The primary endpoint was to assess the safety and tolerability of the combination therapy.
Eight patients (6 men, 2 women) were treated; all eight patients experienced at least one treatment-emergent adverse event (TEAE) of grade ≥3. Dose-limiting toxicities occurred in three patients (37.5%): hepatic hemorrhage (grade 4), blood bilirubin increased (grade 3), and febrile neutropenia (grade 3). Two patients discontinued study because of hepatic hemorrhage (grade 4) and blood bilirubin increase (grade 3). Six deaths occurred due to progressive disease, and no deaths due to TEAEs.
There were no unexpected safety findings with ramucirumab plus FOLFOX4 based on the known safety and toxicity of this regimen. The combination was not sufficiently tolerated in patients with advanced HCC at the specified dose and schedule.
仑伐替尼（静脉注射 8mg/kg，每 2 周 1 次）联合 FOLFOX4 一线治疗晚期肝细胞癌（HCC）的耐受性不足。初步疗效数据表明，该联合方案可能为 HCC 患者带来临床获益。为了进一步开发仑伐替尼联合 FOLFOX 化疗治疗晚期 HCC，应考虑调整剂量和选择患者。
本研究旨在评估仑伐替尼联合 FOLFOX4 一线治疗晚期肝细胞癌（HCC）的安全性、初步疗效、药代动力学和免疫原性。
患者接受仑伐替尼（静脉注射 8mg/kg）治疗，第 1 天，随后给予 FOLFOX4（奥沙利铂 85mg/m 静脉注射，第 1 天；亚叶酸钙 200mg/m 静脉注射，推注氟尿嘧啶[5-FU]400mg/m ，然后 5-FU 600mg/m 持续输注 22 小时，第 1 天和第 2 天），每 2 周 1 次。主要终点是评估联合治疗的安全性和耐受性。
8 例患者（6 例男性，2 例女性）接受了治疗；所有 8 例患者均发生至少 1 次≥3 级治疗相关不良事件（TEAE）。3 例（37.5%）患者出现剂量限制毒性：肝出血（4 级）、血胆红素升高（3 级）和发热性中性粒细胞减少症（3 级）。2 例患者因肝出血（4 级）和血胆红素升高（3 级）停止研究。6 例患者死亡为疾病进展，无因 TEAEs 死亡。
仑伐替尼联合 FOLFOX4 的安全性与该方案已知的安全性和毒性一致，未发现新的安全性问题。在指定剂量和方案下，该联合方案在晚期 HCC 患者中不耐受。
