Phase II study of mitoxantrone and ketoconazole for hormone-refractory prostate cancer.

Background: Doxorubicin plus ketoconazole has exhibited significant activity in patients with advanced prostate cancer. However, overall and cardiac-specific toxicity was reported to be high. Mitoxantrone has activity similar to that of doxorubicin, is less cardiotoxic, and is widely used to treat prostate cancer.

Safety and efficacy of weekly oral oltipraz in chronic smokers.

Cigarette smoking is thought to contribute to carcinogenesis by formation of DNA adducts of tobacco smoke constituents leading to genotoxic damage. The dithiolethione, oltipraz, is a putative cancer chemopreventive agent that induces phase II detoxifying enzymes in preclinical models and reduces aflatoxin adducts in humans living in areas with high dietary levels. To determine if oltipraz could reduce adduct levels of tobacco smoke constituents in the lungs and other target organs, chronic smokers were enrolled to one of three arms: 400 or 200 mg/wk oral oltipraz or placebo.

Phase I pharmacokinetic and pharmacodynamic analysis of unconjugated soy isoflavones administered to individuals with cancer.

Preclinical studies suggest that the isoflavone genistein may have prostate cancer chemopreventive activity. Genistein has been shown to alter cellular levels of protein-tyrosine phosphorylation and is present at high levels in soy. This study was designed to measure the pharmacokinetic parameters of two different preparations of unconjugated soy isoflavones, PTI G-2535 and PTI G-4660 (which contain 43% and 90% genistein, respectively), in human subjects with cancer, to evaluate toxicity and obtain pilot data on in vivo effects on protein-tyrosine phosphorylation.