April 2000: First Clinical Study of Triapine Completed in Cancer Patients
mediconsult.com
Many forms of chemotherapy work by killing fast-growing cells, such as cancer cells. In the process, however, normal cells that grow quickly ? such as skin and blood cells ? are also killed, resulting in the side effects traditionally associated with cancer chemotherapy. But new anticancer drugs are being designed that work through more targeted means, such as interrupting the cellular machinery required to make cancer cells grow and multiply.
One such promising anticancer agent is Triapine, manufactured by Vion Pharmaceuticals, Inc. Vion has announced that the first phase I clinical study of Triapine has just been completed. Triapine has the potential for treating patients with solid tumors and acute myelogenous leukemia. The phase I results showed that Triapine was associated with few side effects, even at the highest dose level.
The development of Triapine is based on the concept that a strong inhibitor of ribonucleotide reductase, an enzyme essential for cells to grow and divide, would be a useful weapon in the therapeutic arsenal against cancer. By inhibiting ribonucleotide reductase, Triapine blocks a critical step in the synthesis of DNA, thereby preventing the growth of tumor cells.
Preclinical studies at Yale University showed that Triapine had promising antitumor activity when it was combined with three well-known and highly potent anticancer agents that damage DNA: etoposide, cisplatinum, and cyclophosphamide. Triapine exhibited significant activity against ovarian cancer, lung cancer, and leukemia in mice.
The phase I trial was conducted at the University of Miami and the Arizona Cancer Research Center. Nine dose levels of Triapine were evaluated in patients who received the drug intravenously as a 2-hour infusion every 4 weeks. The patients tolerated the treatment well at all doses, and the levels of Triapine in their bloodstream were greater than that required for the drug to kill tumor cells, as demonstrated in preclinical studies.
Vion is continuing to enroll patients into a second phase I trial of Triapine given daily for five days every 4 weeks, and will initiate a phase I study of continuous intravenous infusion over a 96-hour period in the near future.
"The extensive preclinical studies conducted by Vion and Yale University to date, combined with these initial clinical results, support our strong belief that Triapine has substantial potential to benefit cancer patients," said Dr. Mario Sznol, Vice President of Clinical Affairs of Vion Pharmaceuticals.
Jim |
