Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland.
Division of Biostatistics and Bioinformatics, Johns Hopkins University, Baltimore, Maryland.
Cancer Res Commun. 2024 Aug 1;4(8):2174-2182. doi: 10.1158/2767-9764.CRC-24-0225.
High-dose intravenous vitamin C (HDIVC) administered to produce pharmacologic concentrations shows promise in preclinical models and small clinical trials, but larger prospective randomized trials are lacking. We evaluated the clinical benefit of combining HDIVC with docetaxel in patients with progressive metastatic castration-resistant prostate cancer (mCRPC). In this double-blind, placebo-controlled phase II trial, 47 patients were randomized 2:1 to receive docetaxel (75 mg/m2 i.v.) with either HDIVC (1 g/kg) or placebo. Coprimary endpoints were PSA50 response and adverse event rates. Secondary endpoints included overall survival, radiographic progression-free survival, and quality of life measured using the Functional Assessment of Cancer Therapy-Prostate instrument. Correlative analyses included pharmacokinetics and oxidative stress markers. Eighty-nine percent of patients previously had three or more lines of therapy. The PSA50 response rate was 41% in the HDIVC group and 33% in the placebo group (P = 0.44), with comparable adverse event rates in both groups. There were no significant differences in Functional Assessment of Cancer Therapy-Prostate scores. The median radiographic progression-free survival was not significantly different between the HDIVC and placebo groups, with durations of 10.1 and 10.0 months (HR, 1.35; 95% confidence interval, 0.66-2.75; P = 0.40), respectively. The median overall survival was 15.2 months in the HDIVC group and 29.5 months in the placebo group (HR, 1.98; 95% confidence interval, 0.85-4.58; P = 0.11). HDIVC did not decrease F2-isoprostanes, indicators of oxidative stress. The study was suspended after prespecified interim analysis indicated futility in achieving primary endpoints. In this patient population, combining HDIVC with docetaxel did not improve PSA response, toxicity, or other clinical outcomes compared with docetaxel alone. Findings do not support the routine use of HDIVC in mCRPC treatment outside of clinical trials.
This is the first randomized, placebo-controlled, double-blind trial to evaluate HDIVC in cancer treatment. The addition of HDIVC to docetaxel in patients with mCRPC does not improve PSA response, toxicity, or other clinical outcomes compared with docetaxel alone. The routine use of HDIVC in mCRPC treatment is not supported outside of clinical trials.
高剂量静脉注射维生素 C（HDIVC）可产生药理浓度，在临床前模型和小型临床试验中显示出前景，但缺乏更大规模的前瞻性随机试验。我们评估了在进展性转移性去势抵抗性前列腺癌（mCRPC）患者中联合 HDIVC 和多西他赛的临床益处。在这项双盲、安慰剂对照的 2 期试验中，47 名患者按 2:1 随机分为多西他赛（75mg/m2，静脉注射）联合 HDIVC（1g/kg）或安慰剂组。主要终点为 PSA50 反应率和不良事件发生率。次要终点包括总生存期、影像学无进展生存期和使用前列腺癌功能评估量表测定的生活质量。相关性分析包括药代动力学和氧化应激标志物。89%的患者之前接受过三线或三线以上的治疗。HDIVC 组 PSA50 反应率为 41%，安慰剂组为 33%（P=0.44），两组不良事件发生率相当。癌症治疗功能评估前列腺量表评分无显著差异。HDIVC 组和安慰剂组的中位影像学无进展生存期无显著差异，分别为 10.1 个月和 10.0 个月（HR，1.35；95%置信区间，0.66-2.75；P=0.40）。HDIVC 组中位总生存期为 15.2 个月，安慰剂组为 29.5 个月（HR，1.98；95%置信区间，0.85-4.58；P=0.11）。HDIVC 不能降低 F2-异前列腺素，这是氧化应激的指标。在预设的中期分析表明主要终点无效后，该研究被暂停。在该患者人群中，与单独多西他赛相比，联合 HDIVC 并不能改善 PSA 反应、毒性或其他临床结局。研究结果不支持在临床试验之外常规使用 HDIVC 治疗 mCRPC。
这是第一项评估癌症治疗中 HDIVC 的随机、安慰剂对照、双盲试验。与单独多西他赛相比，在 mCRPC 患者中联合 HDIVC 并不能改善 PSA 反应、毒性或其他临床结局。临床试验之外不支持常规使用 HDIVC 治疗 mCRPC。
