[HTML][HTML] Phase I clinical trial to evaluate the safety, tolerability, and pharmacokinetics of high-dose intravenous ascorbic acid in patients with advanced cancer
CM Stephenson, RD Levin, T Spector… - Cancer chemotherapy and …, 2013 - Springer
CM Stephenson, RD Levin, T Spector, CG Lis
Cancer chemotherapy and pharmacology, 2013•SpringerPurpose This phase I clinical trial evaluated the safety, tolerability, and pharmacokinetics of
high-dose intravenous (iv) ascorbic acid as a monotherapy in patients with advanced solid
tumors refractory to standard therapy. Methods Five cohorts of three patients received iv
ascorbic acid administered at 1 g/min for 4 consecutive days/week for 4 weeks, starting at 30
g/m 2 in the first cohort. For subsequent cohorts, dose was increased by 20 g/m 2 until a
maximum tolerated dose was found. Results Ascorbic acid was eliminated by simple first …
high-dose intravenous (iv) ascorbic acid as a monotherapy in patients with advanced solid
tumors refractory to standard therapy. Methods Five cohorts of three patients received iv
ascorbic acid administered at 1 g/min for 4 consecutive days/week for 4 weeks, starting at 30
g/m 2 in the first cohort. For subsequent cohorts, dose was increased by 20 g/m 2 until a
maximum tolerated dose was found. Results Ascorbic acid was eliminated by simple first …
Purpose
This phase I clinical trial evaluated the safety, tolerability, and pharmacokinetics of high-dose intravenous (i.v.) ascorbic acid as a monotherapy in patients with advanced solid tumors refractory to standard therapy.
Methods
Five cohorts of three patients received i.v. ascorbic acid administered at 1 g/min for 4 consecutive days/week for 4 weeks, starting at 30 g/m2 in the first cohort. For subsequent cohorts, dose was increased by 20 g/m2 until a maximum tolerated dose was found.
Results
Ascorbic acid was eliminated by simple first-order kinetics. Half-life and clearance values were similar for all patients of all cohorts (2.0 ± 0.6 h, 21 ± 5 dL/h m2, respectively). C max and AUC values increased proportionately with dose between 0 and 70 g/m2, but appeared to reach maximal values at 70 g/m2 (49 mM and 220 h mM, respectively). Doses of 70, 90, and 110 g/m2 maintained levels at or above 10–20 mM for 5–6 h. All doses were well tolerated. No patient demonstrated an objective antitumor response.
Conclusions
Ascorbic acid administered i.v. at 1 g/min for 4 consecutive days/week for 4 weeks produced up to 49 mM ascorbic acid in patient’s blood and was well tolerated. The recommended dose for future studies is 70–80 g/m2.
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