A phase I evaluation of chronotropic delivery of floxuridine by hepatic arterial infusion in patients with metastatic colorectal cancer

Hepatic arterial infusion (HAI) of floxuridine is often used for metastatic colorectal cancer, though this is associated with dose-limiting hepatobiliary toxicity. A phase I trial was initiated to determine if circadian-patterned HAI floxuridine would reduce toxicity. Twenty-one patients were enrolled, and they received a continuous 14-day HAI of floxuridine, with 90-95% of the drug delivered over the same six-hour period daily. The therapy was tolerable, but there was no reduction in hepatobiliary toxicity. The response rate of 33% (1 complete and 6 partial responses) was similar to that of regimens that do not utilize circadian timing. HAI floxuridine chronotherapy for metastatic colorectal cancer cannot be recommended.