Circadian rhythm-modulated chemotherapy with high-dose 5-fluorouracil: a pilot study in patients with pancreatic adenocarcinoma

Eur J Cancer. 1993;29A(13):1851-4. doi: 10.1016/0959-8049(93)90536-o.

Abstract

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.

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adult
  • Aged
  • Circadian Rhythm*
  • Diarrhea / chemically induced
  • Dose-Response Relationship, Drug
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Fluorouracil / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Pancreatic Neoplasms / drug therapy*
  • Pilot Projects
  • Prognosis

Substances

  • Fluorouracil