抗坏血酸、吉西他滨和白蛋白结合型紫杉醇治疗转移性胰腺癌的随机试验。
A randomized trial of pharmacological ascorbate, gemcitabine, and nab-paclitaxel for metastatic pancreatic cancer.
发表日期:2024 Oct 02
作者:
Kellie L Bodeker, Brian J Smith, Daniel J Berg, Chandrikha Chandrasekharan, Saima Sharif, Naomi Fei, Sandy Vollstedt, Heather Brown, Meghan Chandler, Amanda Lorack, Stacy McMichael, Jared Wulfekuhle, Brett A Wagner, Garry R Buettner, Bryan G Allen, Joseph M Caster, Barbara Dion, Mandana Kamgar, John M Buatti, Joseph J Cullen
来源:
Redox Biology
摘要:
转移性胰腺导管腺癌 (PDAC) 患者的 5 年生存率较差。药理学抗坏血酸(P-AscH-,高剂量,静脉注射,维生素 C)已显示出作为化疗辅助药物的前景。我们假设在吉西他滨和白蛋白结合型紫杉醇中添加 P-AscH- 将提高转移性 PDAC 患者的生存率。诊断为 IV 期胰腺癌的患者按 1:1 随机分配至仅吉西他滨和白蛋白结合型紫杉醇(SOC,对照)或 SOC 联合治疗组P-AscH-,75 g,每周 3 次(ASC,研究性)。主要结局是总生存期,次要目标是确定无进展生存期和不良事件发生率。生活质量和患者报告的常见肿瘤症状的结果被视为探索性目标。 36 名参与者被随机分配;其中 34 人接受了指定的研究治疗。所有分析均基于 2023 年 12 月 11 日冻结的数据。静脉注射 P-AscH-可将血清抗坏血酸水平从微摩尔水平升高至毫摩尔水平。添加到吉西他滨白蛋白结合型紫杉醇 (ASC) 中的 P-AscH- 将总生存期延长至 16 个月,而吉西他滨白蛋白结合型紫杉醇 (SOC) 为 8.3 个月(HR = 0.46;90% CI 0.23, 0.92;p = 0.030)。中位无进展生存期为 6.2 个月 (ASC) 对比 3.9 个月 (SOC)(HR = 0.43;90% CI 0.20、0.92;p = 0.029)。添加 P-AscH- 不会对生活质量产生负面影响,也不会增加不良事件的频率或严重程度。转移性胰腺癌患者每周 3 次输注 75 g P-AscH- 可延长总体生存期和无进展生存期,且不会损害治疗质量生命或增加毒性(ClinicalTrials.gov 编号 NCT02905578)。版权所有 © 2024 作者。由 Elsevier B.V. 出版。保留所有权利。
Patients with metastatic pancreatic ductal adenocarcinoma (PDAC) have poor 5-year survival. Pharmacological ascorbate (P-AscH-, high dose, intravenous, vitamin C) has shown promise as an adjunct to chemotherapy. We hypothesized adding P-AscH- to gemcitabine and nab-paclitaxel would increase survival in patients with metastatic PDAC.Patients diagnosed with stage IV pancreatic cancer randomized 1:1 to gemcitabine and nab-paclitaxel only (SOC, control) or to SOC with concomitant P-AscH-, 75 g three times weekly (ASC, investigational). The primary outcome was overall survival with secondary objectives of determining progression-free survival and adverse event incidence. Quality of life and patient reported outcomes for common oncologic symptoms were captured as an exploratory objective. Thirty-six participants were randomized; of this 34 received their assigned study treatment. All analyses were based on data frozen on December 11, 2023.Intravenous P-AscH- increased serum ascorbate levels from micromolar to millimolar levels. P-AscH- added to the gemcitabine + nab-paclitaxel (ASC) increased overall survival to 16 months compared to 8.3 months with gemcitabine + nab-paclitaxel (SOC) (HR = 0.46; 90 % CI 0.23, 0.92; p = 0.030). Median progression free survival was 6.2 (ASC) vs. 3.9 months (SOC) (HR = 0.43; 90 % CI 0.20, 0.92; p = 0.029). Adding P-AscH- did not negatively impact quality of life or increase the frequency or severity of adverse events.P-AscH- infusions of 75 g three times weekly in patients with metastatic pancreatic cancer prolongs overall and progression free survival without detriment to quality of life or added toxicity (ClinicalTrials.gov number NCT02905578).Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.