Role of high-dose vitamin C as adjunct treatment in gastric and colorectal cancers: A systematic review.

Abstract

e15567 Background: Ascorbic acid (Vitamin C), a potent antioxidant, has shown promise in cancer treatment, particularly for colorectal cancer (CRC) and gastric cancer (GC), both major causes of cancer-related deaths. Evidence suggests high-dose vitamin C may inhibit cancer growth, with a synergistic role reported in these malignancies. This review evaluates its impact on CRC and GC treatment outcomes. Methods: Following PRISMA guidelines, a comprehensive literature search was conducted using PubMed, Cochrane, ClinicalTrials.gov, and Embase databases from inception until January 2025. MeSH terms and keywords related to "Colorectal cancer" OR "stomach neoplasms" AND "Ascorbic acid" were used. After screening and removing duplicates, original clinical studies (retrospective and prospective) including patients with confirmed CRC or GC aged ≥18 years were included. Three clinical trials were included. Extracted data included patient demographics, clinical presentation, disease stage, treatment details, and survival outcomes. Included studies were reviewed and described systematically. Results: Three clinical trials involving 262 stage IV CRC (97.7%, n = 256) or GC (2.3%, n = 6) patients were reviewed. Median age ranged from 53 to 60 years (27–78), with ECOG scores of 1 in 40% and 2 in 57.6%. Most patients received ascorbic acid with FOLFOX (97.7%), FOLFIRI (0.38%), or arsenic trioxide (1.9%). In a phase I trial, Wang et al. established the RP2D of ascorbic acid at 1.5 g/kg/day (D1–3) with mFOLFOX6 or FOLFIRI. Combination therapy commonly caused neuropathy (50%), nausea (38.9%), and vomiting (36.1%). A phase III VITALITY trial randomized 442 untreated metastatic CRC patients to FOLFOX ± bevacizumab with (n = 221) or without (n = 221) 1.5 g/kg/day of ascorbic acid (D1–3). No significant differences were found in mPFS (8.6 vs. 8.3 months; HR 0.86, 95% CI 0.70–1.05, p = 0.1), mOS (20.7 vs. 19.7 months; p = 0.7), or ORR (44.3% vs. 42.1%; p = 0.9). Subbarayan et al. (2002) treated 5 refractory metastatic CRC patients with 0.25 mg/kg/day arsenic trioxide and 1000 mg IV vitamin C (5 days/week, 5 weeks). Severe toxicities (fatigue, nausea/vomiting, dehydration) led to trial discontinuation after two cycles, with no complete or partial responses observed. Conclusions: High-dose ascorbic acid has demonstrated potential in inhibiting cancer cell growth in gastrointestinal malignancies, particularly colorectal cancer and gastric cancer. However, clinical trials have shown limited therapeutic benefits, highlighting the need for further research to clarify its role in cancer treatment.