From: High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer
Cancer type (s) | Allocation/Phase | Interventions | VitC IV dosea | VitC dosage and injection scheme | No. patients | Results | Conclusions/Comment | Ref. |
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IVC monotherapy | ||||||||
Advanced cancers | Single group, Phase 1 | IVC monotherapy | high | 30–110 g/m2 (0.8–3.0 g/kg), 4x/week, 4 weeks (both consecutive), rate of 1 g/min | 17 | All doses were well tolerated. Doses of 70, 90, and 110 g/m2 maintained levels at or above 10–20 mM for 5–6 h (Cmax 49 mM). No objective antitumor response | Recommended dose for future studies is 70–80 g/m2 (= 1.9–2.2 g/kg) based on Cmax | |
Single group, Phase 1 | IVC monotherapy | high | 0.4–1.5 g/kg, 3x/week, 4 week treatment cycles; oral dose of 500 mg twice daily on non-infusion days | 24 | Well tolerated, without significant toxicity; dose of 1.5 g/kg sustains plasma ascorbic acid concentrations > 10 mM for > 4 h (Cmax 26 mM); 2 patients with unexpected stable disease | The recommended phase 2 dose is 1.5 g/kg; ascorbate may need to be combined with cytotoxic or other redoxactive molecules to be an efficacious treatment | [12], no ClinicalTrial.gov Identifier | |
Single group, Phase n.s. | IVC monotherapy | medium | 0.15–0.71 g/kg/day, continuous infusion for up to 8 weeks | 24 | IVC therapy relatively safe, only few and minor adverse events observed; plasma ascorbate concentrations in the order of 1 mM attained | Further clinical studies with high dose IVC are warranted | [65], no ClinicalTrial.gov Identifier | |
Prostate | Phase 2 | IVC monotherapy | medium | 5 g week 1, 30 g week 2 and 60 g weeks 3–12; daily oral dose of 500 mg starting after first infusion for 26 weeks | 23 | No patient achieved the primary endpoint of 50% PSA reduction; instead, a median increase in PSA of 17 μg/L was recorded at week 12; no signs of disease remission were observed; target dose of 60 g AA IV produced a peak plasma AA concentration of 20.3 mM [126] | This study does not support the use of intravenous AA outside clinical trials | |
IVC combination therapy - Chemotherapy and radiation therapy | ||||||||
Advanced cancers | Single group, Phase 1/2 | IVC + standard care cytotoxic chemotherapy | high | 1.5 g/kg, 2 or 3x per week | 14 | IVC-chemotherapy is non-toxic and generally well tolerated; individual highly favourable responses found in biliary tract, cervix and head and neck cancer patients, colorectal cancer patients without benefit | Neither proves nor disproves IVC’s value in cancer therapy; illustrates potential for “discovery in clinical practice” | |
Glioblastoma | Single group, Phase 1 | IVC + RT + temozolomide (TMZ) | high | Radiation phase: 15–125 g, 3x weekly, 7 weeks; Adjuvant phase: dose-escalation until plasma level of 20 mM was achieved, 2x weekly, 28 weeks | 13 | Safe and well tolerated; targeted ascorbate plasma levels of 20 mmol/L achieved in the 87.5 g cohort; favourable OS and PFS compared to historical controls (RT + TMZ only) | Phase 2 clinical trial initiated (NCT02344355), currently active, not recruiting | |
NSCLC | Single group, Phase 2 | IVC + carboplatin + paclitaxel | high | 75 g, 2x weekly | 14 | Increased disease control and objective response rates | Still recruiting (NCT02420314), see Table 3 | |
Ovarian | Phase 1/2a, randomized | Arm 1: IVC + carboplatin + paclitaxel Arm 2: carboplatin + paclitaxel only | high | Dose escalation up to 75 or 100 g, with target peak plasma concentration of 350 to 400 mg/dl (20 to 23 mM), 2x/week, for 12 months (of which the first 6 months in conjunction with chemotherapy) | 25 | Longer PFS and substantially decreased toxicities compared to control arm w/o Vit C; trend toward improved median OS | Study not powered for detection of efficacy, larger clinical trials warranted | |
Pancreatic | Single group, Phase 1/2a | IVC + gemcitabine | high | 25–100 g dose escalation in phase I, 75–100 g in phase II, 3x weekly, for 4 weeks | 14 | Well tolerated, no clinically significant influence on gemcitabine pharmacokinetics | Phase 2/3 trial needed to detect efficacy and benefit of IVC | |
Single group, Phase 1 | IVC + RT + gemcitabine | high | 50–100 g daily during RT, 6 weeks | 16 | Safe and well tolerated with suggestions of efficacy; increased OS and PFS compared to institutional average; 100 g determined to be MTD, 75 g selected as a recommended phase II dose | Phase 2 trial is indicated | ||
Phase 2, randomized | Arm 1: IVC + G-FLIP/G-FLIP-DM Arm 2: G-FLIP/G-FLIP-DM only | high | 75–100 g, 1–2x per week, with GFLIP every every 2 weeks until progression | 26 | Safe and well tolerated. May avoid standard 20–40% rates of severe toxicities | Abstract only, no data shown | ||
Single group, Phase 1 | IVC + gemcitabine | high | 50–125 g, 2x weekly to achieve target plasma level of ≥350 mg/dL (≥20 mM) | 9 | Well-tolerated with suggestion of some efficacy; plasma levels of 20–30 mM were reached with doses ranging from 0.75–1.75 g/kg | Phase 2 trial is indicated | ||
IVC combination therapy - Targeted therapy | ||||||||
Colorectal, Gastric | Single group, Phase 1 | IVC + mFOLFOX6 or FOLFIRI (part 1); IVC + mFOLFOX6 ± bevacizumab (part 2) | high | Dose escalation phase (part 1): 0.2–1.5 g/kg, once daily, days 1–3, in a 14-day cycle until MTD was reached; Speed expansion phase (part 2): MTD or at 1.5 g/kg if MTD not reached | 36 (30 colorectal, 6 gastric) | MTD not reached; no DLT; favourable safety profile and preliminary efficacy | Recommended dose for future studies 1.5 g/kg/day; extended to phase 3 study | |
Pancreatic | Single group, Phase 1 | IVC + gemcitabine + erlotinib | high | 50–100 g, 3x/week, 8 weeks | 9 | Tumor shrinkage in 8/9 patients; peak ascorbic acid concentrations as high as 30 mmol/L in the highest dose group | Phase 2 trial with longer treatment period 100 g dosage warranted | |
B-cell non-Hodgkin’s lymphoma | Single group, Phase 1 | IVC + CHASER regimen | high | 75 g or 100 g 5x in 3 weeks | 3 | Whole body dose of 75 g safe and sufficient to achieve an effective serum concentration (> 15 mM (264 mg/dl) | No NCT number; Phase II trial is indicated | [155], no ClinicalTrial.gov Identifier |
IVC combination therapy - Combinations with emerging non-pharmaceutical therapies | ||||||||
NSCLC | Phase 1/2, randomized | Arm 1: IVC + mEHT + BSC Arm 2: BSC alone | high | 1 g/kg, 1.2 g/kg or 1.5 g/kg, 3x/week for 8 weeks (Phase 1); 1 g/kg, 3x/week, 25 treatments in total (Phase 2) | 97 | IVC treatment concurrent with mEHT is safe and improved the QoL of NSCLC patients (Phase 1, Ou et al., 2017); significantly prolonged PFS, OS and QoL (Phase 2) | IVC + mEHT is a feasible treatment in advanced NSCLC |