Systemic infusional chemotherapy for liver metastasis: an improved schedule for 5-fluorouracil

The clinical studies of infusion schedules for cancer chemotherapy have established that this schedule substantially alters the pattern of drug toxicity without necessarily compromising therapeutic effectiveness. Although increased tumor cell killing has not been definitively established, in at least two prospective comparative trials of 5-FU the infusion schedule was superior to bolus delivery in terms of response rate. It is possible that the infusion schedule may be the primary determinant of the effectiveness of hepatic arterial chemotherapy, and preliminary reports of prospective trials comparing systemic infusion with hepatic infusion do suggest that response rates for both routes are similar. An important consideration with regard to infusion schedules is establishing whether or not tumor cell resistance is augmented by the continuous exposure. Almost all chronic disease therapy necessitates maintaining adequate drug levels to ensure disease control including infections, seizure disorders, arthritis, and cardiovascular diseases. For cancer, the intermittent schedule of drug delivery has been dictated by the concept of the primacy of dose and the substantial toxicity associated with these agents. With the technological capability of providing an ambulatory setting for infusion chemotherapy and the substantial modification of toxicity, therapeutic regimens may be more cost effective with the constant infusion schedule.