Phase I clinical trial to evaluate the safety, tolerability, and pharmacokinetics of high-dose intravenous ascorbic acid in patients with advanced cancer

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/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-order kinetics. Half-life and clearance values were similar for all patients of all cohorts (2.0 ± 0.6 h, 21 ± 5 dL/h m(2), respectively). C (max) and AUC values increased proportionately with dose between 0 and 70 g/m(2), but appeared to reach maximal values at 70 g/m(2) (49 mM and 220 h mM, respectively). Doses of 70, 90, and 110 g/m(2) 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/m(2).