BIOAVAILABILITY AND FEASIBILITY OF SUBCUTANEOUS 5-FLUOROURACIL

Continuous intravenous (i.v.) infusion of 5-fluorouracil (5-FU) has be en shown to be superior to bolus regimens in terms of response rates a nd toxicity. However, a continuous infusion is more expensive and pron e to complications such as thromboembolism and infections. A way to ci rcumvent these problems would be to administer 5-FU subcutaneously (s. c.). To assess feasibility and bioavailability of s.c. 5-FU, eight pat ients with advanced cancer received 250 mg 5-FU as an infusion over 90 min either intravenously (i.v.) or s.c. into the abdominal wall. The mean +/- s.d. bioavailability of s.c. 5-FU was 0.89 +/- 0.23. The inte rpatient variability for the area under the plasma concentration-time curve was 48% for the s.c. and 36% for the i.v. infusion. No local sid e effects were observed. To test the local tolerance of a more prolong ed administration three patients received 930-1,000 mg m-2 5-FU by 24- h continuous s.c. infusion. The steady-state plasma levels were compar able to i.v. infusion. One patient developed a painless skin pigmentat ion at the s.c. infusion site. However, the same reaction was observed at the forearm after i.v. infusion. We conclude that at the dose stud ied s.c. 5-FU has an almost complete bioavailability and is well toler ated. Further work will show, whether prolonged s.c. infusion can be u sed as a safe and economical alternative to i.v. infusion.