Circadian rhythm-modulated chemotherapy with high-dose 5-fluorouracil: a pilot study in patients with pancreatic adenocarcinoma.
From November 1986 to April 1989, 16 patients with advanced measurable pancreatic carcinoma were involved in a pilot phase I-II study. 5-Fluorouracil was given every 3 weeks by 5-day continuous chronomodulated venous infusion (CMVI) with peak 5-FU delivery at 4 a.m. Intrapatient dose escalation started at 1200 mg/m2/day up to 1600 mg/m2/day in the absence of grade III (WHO) toxicity. Mucositis and diarrhoea were dose limiting in the 131 cycles given. Three partial responses (21%) and 5 stable diseases were seen in the 14 patients with measurable disease. Dose intensity after three or after six courses (1800 mg/m2/week) was significantly correlated with time to progression (Pearson r = 0.64; P < 0.004). These results, although modest, support a multicentre phase II trial with 5-FU CMVI.
Bertheault-Cvitkovic
F
F
Centre de Chronothérapie, Service des Maladies Sanguines, Immunitaires et Tumorales, Villejuif, France.
Lévi
F
F
Soussan
S
S
Brienza
S
S
Adam
R
R
Itzhaki
M
M
Misset
J L
JL
Bismuth
H
H
D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D002940:Circadian Rhythm; D003967:Diarrhea / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D010865:Pilot Projects; D011379:Prognosis
D005472:Fluorouracil