Phase I clinical trial of i.v. ascorbic acid in advanced malignancy.
BACKGROUND
Ascorbic acid is a widely used and controversial alternative cancer treatment. In millimolar concentrations, it is selectively cytotoxic to many cancer cell lines and has in vivo anticancer activity when administered alone or together with other agents. We carried out a dose-finding phase I and pharmacokinetic study of i.v. ascorbic acid in patients with advanced malignancies.


METHODS
Patients with advanced cancer or hematologic malignancy were assigned to sequential cohorts infused with 0.4, 0.6, 0.9 and 1.5 g ascorbic acid/kg body weight three times weekly.


RESULTS
Adverse events and toxicity were minimal at all dose levels. No patient had an objective anticancer response.


CONCLUSIONS
High-dose i.v. ascorbic acid was well tolerated but failed to demonstrate anticancer activity when administered to patients with previously treated advanced malignancies. The promise of this approach may lie in combination with cytotoxic or other redox-active molecules.
Montreal Centre for Experimental Therapeutics in Cancer, Lady Davis Institute for Medical Research, McGill University and the Jewish General Hospital, Montreal, Quebec, Canada. l.hoffer@mcgill.ca
L J
LJ
Hoffer
M
M
Levine
S
S
Assouline
D
D
Melnychuk
S J
SJ
Padayatty
K
K
Rosadiuk
C
C
Rousseau
L
L
Robitaille
W H
WH
Miller
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy*
D000975:Antioxidants; D001205:Ascorbic Acid