Timing of cancer chemotherapy based on circadian variations in tumor tissue blood flow

Abstract

Blood flows of normal tissues (subcutis, liver, kidney cortex, bone marrow) and tumor tissues (SLC) were measured during a daytime period (3-9 HALO) and a nighttime period (15-21 HALO) by the hydrogen clearance technique. Rats were subjected to an artificial light-dark cycle with light from 7 A.M. to 7 P.M. In all normal tissues, there were no significant differences between average tissue blood flows in 2 different time zones, while tumor tissue blood flow increased significantly in the nighttime. Based on this functional characteristic of tumor microcirculation, anti-tumor effects were compared between a group in which ADM was administered at 4 HALO and a group in which it was administered at 16 HALO. The therapeutic effect of ADM on rats administered at 16 HALO was significantly greater, particularly in large tumors, than that on rats administered at 4 HALO. The main reason for this therapeutic improvement may be due to the selective increase in delivery of anti-cancer drugs to tumor tissues brought about by a circadian increase in tumor tissue blood flow.