关于vc抗癌--从两个临床试验谈起

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VC抗癌说由来已久，众说纷纭；但大多是细胞、动物试验或个例报告，不足为凭。

现搜集整理两个VC抗癌的临床试验如下，据此加以研判：

1、《A Randomized, Open-Label, Multicenter, Phase 3 Study of High-Dose Vitamin C Plus FOLFOX ± Bevacizumab versus FOLFOX ± Bevacizumab in Unresectable Untreated Metastatic Colorectal Cancer (VITALITY Study)》

这应该是到目前为止，涉及到VC抗癌的，规模最大的一个随机对照试验。

Patients and methods: Between 2017 and 2019, histologically confirmed patients with mCRC (n = 442) with normal glucose-6-phosphate dehydrogenase status and no prior treatment for metastatic disease were randomized (1:1) into a control (FOLFOX ± bevacizumab) and an experimental [high-dose vitamin C (1.5 g/kg/d, intravenously for 3 hours from D1 to D3) plus FOLFOX ± bevacizumab] group. Randomization was based on the primary tumor location and bevacizumab prescription.

试验结果：The progression-free survival (PFS) of the experimental group was not superior to the control group [median PFS, 8.6 vs. 8.3 months; HR, 0.86; 95% confidence interval (CI), 0.70-1.05; P = 0.1]. The objective response rate (ORR) and overall survival (OS) of the experimental and control groups were similar (ORR, 44.3% vs. 42.1%; P = 0.9; median OS, 20.7 vs. 19.7 months; P = 0.7). Grade 3 or higher treatment-related adverse events occurred in 33.5% and 30.3% of patients in the experimental and control groups, respectively.

这个临床试验结果意味着即便是采用了静脉注射的给药方式，即便是用了1.5 g/kg/d这么高的剂量（一个50公斤的患者一天要静脉注射75克之多的VC），从整体而言，传统化疗靶向抗癌治疗增加IVC，也没有给疗效带来有统计学意义上的改善。

但是，“In prespecified subgroup analyses, patients with RAS mutation had significantly longer PFS (median PFS, 9.2 vs. 7.8 months; HR, 0.67; 95% CI, 0.50-0.91; P = 0.01) with vitamin C added to chemotherapy than with chemotherapy only.”

在RAS突变（kras、hras、nras）患者中，应用静脉注射大剂量VC，却带来了PFS的统计学意义上的显著改善。

研究者认为这个结果也是跟临床前研究结论相符的：“It suggested that the oxidized form of vitamin C, dehydroascorbate, was the pharmaceutically active agent resulting in an energy crisis and colorectal cancer cell death, and the selective cytotoxicity of vitamin C stemmed from high expression of GLUT1 glucose transporter combined with RAS oncogene-induced glycolytic addiction”

另外在超过55岁的老年患者中也带来了PFS上的益处。这或许跟老年患者中VC缺乏比例高（88%）有一定的关系。

研究者认为临床设计上有两个不足：“First, the patients received intravenous high-dose vitamin C for 3 days of every treatment cycle, which might not be enough for vitamin C to show its antitumor effect.”“Second, high-dose vitamin C discontinued at 6 months before the majority of patients progressed, and the true impact of high-dose vitamin C in mCRC may thus be underestimated.”

核心意思就是尽管IVC的单日剂量不小，但是打的天数不多，治疗积累的总量并不算很多，有可能没有让VC发挥出应有的作用来。

从这个临床试验结果来看，VC要发挥抗癌作用，关键在于患者的基因突变情况，在于患者的VC缺乏情况，在于VC的给药方式、剂量、剂型、给药频率的情况。不能脱离这些具体条件去得出什么结论。

下面这个临床试验也说明了这点。

2、《Randomized trial of topical ascorbic acid in DMSO versus imiquimod for the treatment of basal cell carcinoma》

这是到目前为止，VC抗癌疗效最好的一个临床试验。

“The objective of this study was to compare efficacy of a topical solution consisting of 30% ascorbic acid in 95% dimethylsulfoxide with topical imiquimod in the treatment of basal cell carcinoma. Twenty-five patients with 29 biopsy confirmed basal cell carcinomas were randomly assigned to receive either the topically applied ascorbic acid treatment twice daily for 8 weeks or topical imiquimod, a standard and well characterized topical treatment. ”

试验结果：“After 8 weeks, post-treatment biopsy of lesions showed complete resolution of 13/15 (86.7%) in the ascorbic acid group, while 8/14 (57.1%) lesions in the IMQ group were resolved (p < 0.05 Chi Square). Topical ascorbic acid was superior at 8 weeks, and non-inferior at 12 weeks to topical imiquimod in the treatment of low risk nodular and superficial lesions. In addition, ascorbic acid was associated with fewer adverse effects than imiquimod. 70% of patients in the imiquinod group showed residual hypopigmentation at 30mo follow up versus 0% in the ascorbate group.”

剂型上把ascorbic acid 溶在 DMSO这个渗透力极强的无毒的佐剂里，给药方式上采用涂抹这种药物直接接触病灶的方式，这样保证了药物在病灶内的局部高浓度，这是临床试验成功的关键。

按照这两个临床试验的思路，完成可以拓展VC-DMSO药液对RAS突变患者或者严重缺乏VC患者病灶实施病灶表面给药或者瘤体内直接给药的治疗。