The camptothecins are a new class of chemotherapeutic radiation sensitizers
, Clinical trials with camptothecins alone show higher toxicity than predic
ted by preclinical models, which has created the challenge of finding new w
ays to widen the therapeutic window, Camptothecin dose, schedule, and timin
g 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 ear
ly phase I and II chemoradiation trials, including a multicenter, phase II
study planned by the Radiation Therapy Oncology Group (RTOG) in operable re
ctal cancer using irinotecan (CPT-II, Camptosar), One novel approach (based
on preclinical observations) with the potential to widen the therapeutic w
indow may be the use of a chronomodulated camptothecin delivery schedule wi
th irradiation.