[Continuous double administration of 5 fluorouracil (intravenous and intraperitoneal) modulated by folinic acid: phase I clinical study and pharmacokinetics in patients with intra-abdominal developing cancers].
Thirteen patients with intra-abdominal malignancies entered a phase I study of fluorouracil (5-FU) given by continuous infusion (96 h) iv and ip, simultaneously, and modulated by high-dose folinic acid-iv. Severe but reversible stomatitis was the only dose-limiting toxicity at a dose of 5-FU of 550 mg/m2/day. Local toxicity (5-FU-induced abdominal pain) was a significant side effect in patients receiving more than 1 cycle. The pharmacokinetic advantage of 5-FU-ip was confirmed in our study (ratio AUC peritoneum/plasma between 160 and 328). The systemic exposure to 5-FU (plasmatic AUC ranging from 73.4 to 173.21 microM) and to AF were found in efficacious ranges. The recommended dose of 5-FU iv and ip is 500 mg/m2/day. This regimen is feasible and may potentially have application for adjuvant chemotherapeutic programs after surgery for colorectal cancer.
de Forni
M
M
Groupe de pharmacologie clinique et expérimentale des médicaments anticancéreux, centre Claudius-Regaud, Toulouse, France.
Gualano
V
V
Canal
P
P
Martel
P
P
Izar-Soum
F
F
Chevreau
C
C
Soulié
P
P
Roché
H
H
Bugat
R
R
D000008:Abdominal Neoplasms / Q000188:drug therapy*; D004357:Drug Synergism; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D007262:Infusions, Intravenous; D007274:Injections, Intraperitoneal; D002955:Leucovorin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy
D002955:Leucovorin; D005472:Fluorouracil
5-fluorouracile en perfusion continue double voie (intraveineuse et intrapéritonéale) modulé par l'acide folinique: étude clinique de phase I et pharmacocinétique chez des patients porteurs de cancers à évolution intra-abdominale.