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Background. The use of ambulatory infusions of 5-fluorouracil (5-FU) improves the therapeutic index of this drug and is superior to the traditional schedule of bolus administration weekly or daily for 5 days at 5-week intervals. The infusion schedules that have been used vary as follows: (1) 24-hour infusion weekly; (2) 48-hour infusion weekly or biweekly; (3) 120-hour infusion at 4-5-week intervals; (4) 14-day infusion; and (5) protracted infusions continuously for 10 weeks or more. The relationship of dose intensity to infusion duration and the analysis of costs of chemotherapy were reviewed. Methods. Selected clinical trials of infusional 5-FU were analyzed regarding infusion duration and dose intensity in relationship to response rates (RR). Chemotherapy cost was analyzed distinguishing 'cost' definitions. Results. The response rates for the infusion durations studied in Phase II and III trials were: (1) 24 hours, 25%; (2) 48 hours, 30%; (3) 120 hours, 3%; (4) 14-day, 12%; and (5) 10 weeks, 30%. The corresponding DI for each infusion duration was (1) 24 hours, 2.6 g/[m.sup.2]/week; (2) 48 hours, 2.4 g/[m.sup.2]/week; (3) 120 hours, 1.25 g/[m.sup.2]/week; (4) 14-days, 1.225 g/[m.sup.2]/week; and (5) 10 weeks, 2.1 g/[m.sup.2]/week. Cost analysis by actual reimbursement was compared for 5-FU infusion and bolus 5-FU with leucovorin (high and low dose) and 5-FU with interferon. Monthly reimbursement for each is $1400, $2000, and $1150, and up to $3000, respectively. Conclusions. DI and infusion duration have a complex interaction that may contribute meaningfully to the therapeutic index, but this issue can only be resolved by randomized clinical trials. The cost of 5-FU infusion is comparable to that of bolus therapy when leucovorin or interferon are added in combination. Considering the relative absence of patient toxicity, the costs of 5-FU infusion are substantially less than bolus delivery. Cancer 1992; 70:998-1002.

6-Mercaptopurine (6-MP) is a cycle specific antineoplastic agent with a short serum half-life following bolus administration, providing a rationale for continuous infusional administration of the parenteral formulation. 22 patients received 38 courses of 14 day 6-MP infusion. The maximum tolerated dose (MTD) was 35mg/m2/day (total dose per 14 day cycle 490mg/m2) with cycles repeated at 28 days. Toxicities included transient hyperbilirubinaemia, leucopenia and thrombocytopenia. 13 evaluable patients with advanced colon cancer resistant to 5-fluorouracil with or without leucovorin received infusional 6-MP at the MTD as part of the phase II study analysis, but no objective responses were observed. Phase II studies in previously untreated patients and longer infusion durations are being evaluated.