Chronic dosing of oltipraz in people at increased risk for colorectal cancer

Cancer Detect Prev. 2001;25(4):352-61.


The dithiolethione oltipraz is being developed as a chemopreventive agent for many malignancies, including colorectal cancer, on the basis of its in vivo protective activity against chemically induced tumors in a variety of animal models. This protection has been associated with an enhanced capacity to detoxify reactive carcinogens and, more recently, with increased DNA repair. In a previous single-dose study, elevated detoxification gene expression was observed in the days after oltipraz dosing. Now, in this clinical study, we evaluated the effects of oltipraz when given over a 3-month period. Fourteen individuals with increased risk for colorectal cancer were randomly assigned to one of two oral doses (125 or 250 mg/m2) of oltipraz twice weekly for 12 weeks. Two of seven subjects at the 250 mg/m2 dosage required dose reductions, owing to significant fatigue. The 125 mg/m2 dose level was well tolerated by all patients. Blood or colon tissue (or both) for evaluation of glutathione, glutathione S-transferase, DT-diaphorase activity, and DT-diaphorase mRNA expression were obtained prior to treatment and at weeks 6, 12, and 16. No significant modulation of phase II detoxification enzymes was seen at either dose studied during this period. Phase II trials evaluating a tolerable regimen of oltipraz (as demonstrated in this study) and other possible mechanisms that may be responsible for the protective activity of oltipraz should be pursued.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anticarcinogenic Agents / administration & dosage
  • Anticarcinogenic Agents / therapeutic use*
  • Biomarkers, Tumor / blood
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / prevention & control
  • Enzyme Induction / drug effects
  • Female
  • Glutathione / blood
  • Glutathione Transferase / biosynthesis
  • Humans
  • Male
  • Middle Aged
  • NAD(P)H Dehydrogenase (Quinone) / biosynthesis
  • Pyrazines / administration & dosage
  • Pyrazines / therapeutic use*


  • Anticarcinogenic Agents
  • Biomarkers, Tumor
  • Pyrazines
  • oltipraz
  • NAD(P)H Dehydrogenase (Quinone)
  • Glutathione Transferase
  • Glutathione