title: Phase I clinical trial to evaluate the safety, tolerability, and pharmacokinetics of high-dose intravenous ascorbic acid in patients with advanced cancer.
abstract: OBJECTIVE
  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.
authors.affiliation: Cancer Treatment Centers of America®, Zion, IL 60099, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Stephenson
authors.forename: Robert D
authors.initials: RD
authors.lastname: Levin
authors.forename: Thomas
authors.initials: T
authors.lastname: Spector
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Lis
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D000975:Antioxidants / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D001205:Ascorbic Acid / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D015331:Cohort Studies; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009367:Neoplasm Staging; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011788:Quality of Life
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D001205:Ascorbic Acid