F. Bertheaultcvitkovic et al., CIRCADIAN RHYTHM-MODULATED CHEMOTHERAPY WITH HIGH-DOSE 5-FLUOROURACIL- A PILOT-STUDY IN PATIENTS WITH PANCREATIC ADENOCARCINOMA, European journal of cancer, 29A(13), 1993, pp. 1851-1854
From November 1986 to April 1989, 16 patients with advanced measurable
pancreatic carcinoma were involved in a pilot phase I-II study. 5-Flu
orouracil 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 phas
e II trial with 5-FU CMVI.