Department of Medicine, The University of Hong Kong, Pok Fu Lam, Hongkong.
Bio-Cancer Treatment International Ltd, Shatin, Hongkong.
Invest New Drugs. 2022 Apr;40(2):314-321. doi: 10.1007/s10637-021-01178-3. Epub 2021 Nov 4.
We investigated the safety and efficacy of a pegylated arginase (PEG-BCT-100) in combination with chemotherapy (oxaliplatin and capecitabine) [PACOX] in advanced HCC patients.
This was a single centre phase 1 trial to assess the safety and tolerability of PACOX. All the enrolled subjects received treatment in 3-weekly cycles: intravenous PEG-BCT-100 2.7 mg/kg on days 1, 8 and 15 of each cycle; oral capecitabine 1000 mg/m twice daily on day 1-14 of each cycle and intravenous oxaliplatin on day 1. Three dose levels of oxaliplatin (85 mg/m, 100 mg/m or 130 mg/m) were studied to define the maximum tolerated dose (MTD). Adverse events (AEs), efficacy by RECIST v1.1, time to progression (TTP), progression-free survival (PFS) and overall survival (OS) were studied.
Seventeen patients were enrolled at 3 dose levels of oxaliplatin: 85 mg/m (8 patients), 100 mg/m (3 patients), and 130 mg/m (6 patients). The median age was 55 years; all had had locoregional chemotherapy or targeted therapy such as sorafenib, but no systemic chemotherapy. The most common AEs were nausea (82%), injection site reaction (76%), palmar-plantar erythrodysesthesia (59%), oral mucositis (53%) and vomiting (53%). There was no dose-limiting toxicity (DLT). Median duration on study was 8 weeks overall. In 14 evaluable cases, one achieved partial response (PR), 4 had stable disease (SD); disease control rate was 36%; most responses were observed in the 130 mg/m cohort with 1 PR and 2 SDs. Median TTP and PFS were both 7.0 weeks. Overall median OS was 10.7 months; the median OS was not reached at 19.4 months of follow-up in the 130 mg/m2 cohort.
The PACOX regimen demonstrated good anti-cancer activity and survival advantage in advanced pre-treated HCC with favourable safety profile. It warrants further phase II/III studies.
我们研究了聚乙二醇化精氨酸酶（PEG-BCT-100）联合化疗（奥沙利铂和卡培他滨）[PACOX]在晚期 HCC 患者中的安全性和疗效。
这是一项单中心的 1 期试验，旨在评估 PACOX 的安全性和耐受性。所有入组患者均接受 3 周为 1 个周期的治疗：静脉注射 PEG-BCT-100 2.7mg/kg，分别于每个周期的第 1、8 和 15 天；卡培他滨 1000mg/m，每天 2 次，每个周期的第 1-14 天；奥沙利铂于第 1 天静脉给药。研究了三种奥沙利铂剂量水平（85mg/m、100mg/m 和 130mg/m），以确定最大耐受剂量（MTD）。研究了不良事件（AE）、RECIST v1.1 评估的疗效、无进展生存期（PFS）、进展时间（TTP）和总生存期（OS）。
17 例患者入组，分别接受了 3 种奥沙利铂剂量水平的治疗：85mg/m（8 例）、100mg/m（3 例）和 130mg/m（6 例）。中位年龄为 55 岁；所有患者均接受过局部化疗或索拉非尼等靶向治疗，但未接受过系统化疗。最常见的 AE 是恶心（82%）、注射部位反应（76%）、掌跖红斑感觉迟钝（59%）、口腔粘膜炎（53%）和呕吐（53%）。无剂量限制毒性（DLT）。总体中位研究时间为 8 周。在 14 例可评估病例中，1 例部分缓解（PR），4 例疾病稳定（SD）；疾病控制率为 36%；最有反应的是在 130mg/m2 组，有 1 例 PR 和 2 例 SD。中位 TTP 和 PFS 均为 7.0 周。总中位 OS 为 10.7 个月；130mg/m2 组中位 OS 未达到，19.4 个月的随访时仍存活。
PACOX 方案在晚期预处理 HCC 患者中显示出良好的抗肿瘤活性和生存优势，且安全性良好。值得进一步开展 II/III 期研究。
