Tumour blood flow influences combined radiation and doxorubicin treatments

Abstract

Background and purpose: Doxorubicin is usually an effective radiosensitizer in vitro, but in vivo reports have been more variable. We have examined potential explanations for those observations by comprehensively evaluating doxorubicin and radiation treatments in xenografted human 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 combination with cell sorting, laser Doppler flowmetry, and the dual staining mismatch technique. Results: Doxorubicin decreased tumour blood flow in all tumour systems, in a dose-dependent fashion with each assay. This resulted in increased tumour hypoxia and decreased response to radiation 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 effects of doxorubicin on tumour blood flow contraindicate its administration immediately prior to irradiation.