ArticleBMC cancer2019
Phase I study of high-dose ascorbic acid with mFOLFOX6 or FOLFIRI in patients with metastatic colorectal cancer or gastric cancer.
Article in BMC cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02969681 (A Randomized Phase Ⅲ Study of IV Ascorbic Acid in Combination With FOLFOX+/- Bevacizumab vs Treatment With FOLFOX+/- Bevacizumab Alone as First-line Therapy for Advanced Colorectal Cancer), which is not on this map. Cited by 32 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomized Phase Ⅲ Study of IV Ascorbic Acid in Combination With FOLFOX+/- Bevacizumab vs Treatment With FOLFOX+/- Bevacizumab Alone as First-line Therapy for Advanced Colorectal Cancer
Who cites it
32 citing papers in PubMed, 2 syntheses or guidelines pooled it, 55 citations in OpenAlex.
- Effect of vitamins C and E on cancer survival; a systematic review.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2022Pooled it
- Preventing Colitis-Associated Colon Cancer With Antioxidants: A Systematic Review.Cellular and molecular gastroenterology and hepatology · 2021Pooled it
- 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).Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- Sensitizing Colorectal Cancer to PARP Inhibitors: Biomarkers, Mechanisms, and Combination Strategies.International journal of molecular sciences · 2026Review
- Immune, molecular and genetic profiles of gastric signet ring cell carcinoma: Recent progress and future challenges.International journal of cancer · 2026Review
- The Redox Paradox of Natural Supplements in Cancer: A Narrative Review to Guide Clinical Practice.Antioxidants (Basel, Switzerland) · 2026Review
- High-dose vitamin C: A promising anti-tumor agent, insight from mechanisms, clinical research, and challenges.Genes & diseases · 2026Review
- Review
- High-dose vitamin C as a metabolic treatment of cancer: a new dimension in the era of adjuvant and intensive therapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Post-diagnostic multivitamin supplement use and colorectal cancer survival: A prospective cohort study.Cancer · 2024Article
- The Involvement of Ascorbic Acid in Cancer Treatment.Molecules (Basel, Switzerland) · 2024Review
- Metabolic targeting of malignant tumors: a need for systemic approach.Journal of cancer research and clinical oncology · 2023Review
- Overcoming EGFR Resistance in Metastatic Colorectal Cancer Using Vitamin C: A Review.Biomedicines · 2023Review
- Resistance to targeted therapy in metastatic colorectal cancer: Current status and new developments.World journal of gastroenterology · 2023Review
- Can plasma vitamin C predict survival in stage IV colorectal cancer patients? Results of a prospective cohort study.Frontiers in nutrition · 2023Article
- Role of vitamins A, C, D, E in cancer prevention and therapy: therapeutic potentials and mechanisms of action.Frontiers in nutrition · 2023Review
- Ascorbate as a Bioactive Compound in Cancer Therapy: The Old Classic Strikes Back.Molecules (Basel, Switzerland) · 2022Review
- High-Dose Vitamin C for Cancer Therapy.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Evaluation of CSTB and DMBT1 expression in saliva of gastric cancer patients and controls.BMC cancer · 2022Article
- The Result of Vitamin C Treatment of Patients with Cancer: Conditions Influencing the Effectiveness.International journal of molecular sciences · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 1 institution in 1 country.
Funding
Abstract
backgroundPreclinical studies suggest synergistic effectiveness of ascorbic acid (AA, vitamin C) and cytotoxic agents in gastrointestinal malignancies. This phase 1 study aimed to establish the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of AA combined with mFOLFOX6 or FOLFIRI regimens in patients with metastatic colorectal cancer (mCRC) or gastric cancer (mGC).
methodsIn the dose-escalation phase, patients received AA (0.2-1.5 g/kg, 3-h infusion, once daily, days 1-3) with mFOLFOX6 or FOLFIRI in a 14-day cycle until the MTD was reached. In the speed-expansion phase, AA was administered at the MTD or at 1.5 g/kg if the MTD was not reached at a fixed rate of 0.6, 0.8 or 1 g/min. Pharmacokinetics and preliminary efficacy were also assessed.
resultsThirty-six patients were enrolled. The MTD was not reached. The RP2D was established as AA at 1.5 g/kg/day, days 1-3, with mFOLFOX6 or FOLFIRI. No dose-limiting toxicity (DLT) was detected during dose escalation. The most common treatment-emergent adverse events (TRAEs) were sensory neuropathy (50%), nausea (38.9%), vomiting (36.1%) and neutropenia (27.8%). Grade 3-4 TRAEs were neutropenia (13.9%), sensory neuropathy (2.8%), vomiting (2.8%), diarrhea (2.8%) and leukopenia (2.8%). AA exposure was dose-proportional. The objective response rate was 58.3%, and the disease control rate was 95.8%. No difference in efficacy was found between mCRC patients with wild-type RAS/BRAF and mutant RAS or BRAF.
conclusionsThe favorable safety profile and preliminary efficacy of AA plus mFOLFOX6/FOLFIRI support further evaluation of this combination in mCRC or mGC.
trial registrationClinicalTrial.gov Identifier: NCT02969681 .
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.