Terminated, 9/12/2001. Survival following radiotherapy for glioblastoma remains limited to 9 to 12 months. Agents which inhibit DNA repair represent a novel class of radiosensitizers which are currently being explored in the treatment of Glioblastoma. Hydroxyurea (Hu) is a recognized radiosensitizer which is not commercially available in an iv preparation for continuous infusion. In vitro data supporting the various possible mechanisms of radiosensitization including DNA repair inhibition, suggest that this agent would be most effective if a treated tumor were exposed to steady rather than bolus concentrations. In addition, its rapid half life and clearance would require frequent oral dosing to achieve steady state concentrations. We are thus administering Hu as a continuous IV infusion. Hu is synergistic with other repair inhibitors such as Ara-c, Ara-a, and Pentoifylline (PTF). PTF is a methylxanthine analog with hemorrheologic activity which is a potent radiosensitizer and repair inhibitor in vitro. In this study, Hu is being given via continuous infusion with PTF in a phase I dose escalation of PTF to patients receiving twice daily radiotherapy for glioblastoma.
