Controversial issues in 5-fluorouracil infusion use. Dose intensity, treatment duration, and cost comparisons.
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/m2/week; (2) 48 hours, 2.4 g/m2/week; (3) 120 hours, 1.25 g/m2/week; (4) 14-days, 1.225 g/m2/week; and (5) 10 weeks, 2.1 g/m2/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.
Anderson
N
N
Cancer Center, New England Baptist Hospital, Boston, Massachusetts 02120.
Lokich
J
J
D003365:Costs and Cost Analysis; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005472:Fluorouracil / Q000008:administration & dosage* / Q000191:economics; D006801:Humans; D007263:Infusions, Parenteral / Q000191:economics*
D005472:Fluorouracil