RADIOENHANCEMENT BY CISPLATIN WITH ACCELERATED FRACTIONATED RADIOTHERAPY IN A HUMAN TUMOR XENOGRAFT

The aim of the present study was to investigate whether cisplatin woul d enhance the radioresponse of a human tumour xenograft when given in different schedules combined with accelerated fractionated radiation t herapy. A human squamous carcinoma of the hypopharynx, FaDu, was grown in the thigh of athymic nude mice. Tumours were exposed to twice-dail y 2-Gy fractions, applied 6 h apart over 2 weeks, 5 days a week, alone or combined with cisplatin given at maximally tolerated doses in thre e different schedules: (I) i,p. as a single bolus (SE) or (2) i,p. as a daily bolus at 30 min before the first daily radiation fraction or ( 3) s.c. as a continuous infusion through a mini-osmotic pump over 13 d ays, commencing 24 h prior to the first daily radiation fraction. The end point for the study was tumour growth delay (TGD), calculated as t he difference between the delay in regrowth to 200% of the initial tum our size in treated versus control mice. SE cisplatin plus radiation s howed only all additive effect on TGD, whereas daily-bolus and continu ous-infusion cisplatin demonstrated a greater than additive effect whe n combined with accelerated fractionated radiation in this human tumou r model. Cisplatin appears to be especially beneficial as a radiation enhancer when given throughout the course of radiation.