A phase I study of intravenous azimexon therapy in human cancer

Azimexon, a synthetic derivative of the 2-cyanaziridines, was given intravenously daily for 5 days to 19 cancer patients in a Phase I trial designed to determine the drug's tolerable dose, toxicity, and effects on immune and nonimmune host defense parameters. No myelosuppression, neurologic, renal, hepatic, or gastrointestinal toxicities could be detected. The only toxic side effect observed after 5 days of intravenous azimexon was a self-limiting dose-dependent hemolysis. Absolute lymphocyte count (ALC) increased from a pretreatment value of 0.96 × 10³μl to 1.56 × 10³/μl on day 21 (p < 0.05). This increase was induced primarily by the less hemolytic 200–250 mg/m² doses of azimexon. Among 12 patients given this lower dosage, ALC increased from an average initial value of 0.90 × 10³/μl to 1.86 × 10³/μl on day 21 (p < 0.01). Absolute number of OKT3⁺ cells increased from 0.524 to 0.914 × 10³/μl (p < 0.05) with lower drug doses. The mean absolute number of OKT4⁺ cells increased from 0.294 on day 0 to 0.574 × 10³/μl on day 21 (p < 0.05), and the number of OKT8⁺ cells increased from 0.202 to 0.388 × 10³/μl, with no significant changes in helper/suppressor ratio. Significant increases in mitogenic responses to phytohemagglutinin (PHA) [from 13.4 to 35.7 × 10³ net cpm (p < 0.05)] and to concanavalin A (con A) [from 6.4 to 25.6 × 10³ net cpm (p < 0.05)] were also observed with higher drug doses. Azimexon may have a role in managing cancer-associated dysregulation of the immune response.