Camptothecin schedule and timing of administration with irradiation

The camptothecins are a new class of chemotherapeutic radiation sensitizers. Clinical trials with camptothecins alone show higher toxicity than predicted by preclinical models, which has created the challenge of finding new ways to widen the therapeutic window. Camptothecin dose, schedule, and timing with irradiation are important factors that need to be considered in the design of new studies with these S-phase agents. Data are reviewed from early phase I and II chemoradiation trials, including a multicenter, phase II study planned by the Radiation Therapy Oncology Group (RTOG) in operable rectal cancer using irinotecan (CPT-11, Camptosar). One novel approach (based on preclinical observations) with the potential to widen the therapeutic window may be the use of a chronomodulated camptothecin delivery schedule with irradiation.