TUMOR BLOOD-FLOW INFLUENCES COMBINED RADIATION AND DOXORUBICIN TREATMENTS

Background and purpose: Doxorubicin is usually an effective radiosensi tizer in vitro, but in vivo reports have been more variable. We have e xamined potential explanations for those observations by comprehensive ly evaluating doxorubicin and radiation treatments in xenografted huma n tumours, and in conventional mice with syngeneic tumours. Materials and methods: Nude or SCID mice bearing the SiHa cervical squamous cell carcinoma or WiDr colon adenocarcinoma were studied, as were C3H/HeN animals with SCCVII tumours. Assays included a clonogenic assay in com bination with cell sorting, laser Doppler flowmetry, and the dual stai ning mismatch technique. Results: Doxorubicin decreased tumour blood h ow in all tumour systems, in a dose-dependent fashion with each assay. This resulted in increased tumour hypoxia and decreased response to r adiation when inappropriate treatment sequences were employed. However , significant variability from animal to animal was noted. Conclusions : To the extent that these results can be extrapolated to human tumour treatments, we conclude that unless compelling evidence suggests that a tumour will be exceedingly sensitive to the drug, the potential eff ects of doxorubicin on tumour blood flow contraindicate its administra tion immediately prior to irradiation. (C) 1997 Elsevier Science Irela nd Ltd.