A pharmacokinetic study of 5-FU/leucovorin and alpha-interferon in advanced cancer.
The present study was designed to study 5-FU pharmacokinetics after interferon. Weekly bolus 5-FU (500 mg/m2), immediately followed by leucovorin (60 mg/m2) was given in 14 weekly cycles to 55 gastrointestinal and breast cancer patients. Interferon-alpha was given on days 2, 4 and 6, starting from cycle 2 at a dose of 0.5 million units (MU) and stepwise increased to 12 MU in cycles 12 and 13. Five patients could not tolerate the treatment even at the lowest dose of interferon and 22 patients were unavailable for the pharmacokinetic analysis because of dose reductions of 5-FU. Five patients were able to follow the protocol to 12 MU, whereas most patients were unable to continue owing to toxicity. 5-FU pharmacokinetics was analysed every second cycle. Peak concentration and AUC were increased after 12 MU of interferon, but no other significant influence of interferon on pharmacokinetic parameters of 5-FU was observed.
Larsson
P A
PA
Department of Surgery, Lasarettet Helsingborg, Sweden. per-anders.larsson@nvs.ltskane.se
Glimelius
B
B
Jeppsson
B
B
Jönsson
P E
PE
Malmberg
M
M
Gustavsson
B
B
Carlsson
G
G
Svedberg
M
M
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003131:Combined Modality Therapy; D004347:Drug Interactions; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000494:pharmacology*; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged
D000964:Antimetabolites, Antineoplastic; D016898:Interferon-alpha; D002955:Leucovorin; D005472:Fluorouracil