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Cancer Chemother Pharmacol. 2002 Mar;49(3):235-43. Epub 2002 Jan 16.

Influence of oxaliplatin on 5-fluorouracil plasma clearance and clinical consequences.

Author information

1
Department of Medical Oncology and Clinical Pharmacology, Centre Paul Papin, Centre Régional de Lutte Contre le Cancer, 49000 Angers cedex, France.

Abstract

The influence of oxaliplatin (OXA) on 5-fluorouracil (5-FU) plasma clearance was investigated.

PATIENTS AND METHODS:

A group of 29 patients with advanced colorectal cancer refractory to prior weekly 8-h 5-FU infusion plus bolus folinic acid (FA), received the same combination plus OXA at 130 mg/m(2) every 3 weeks, OXA plus 5-FU plus FA on day 1, and 5-FU plus FA on days 8 and 15. Steady-state 5-FU concentrations in plasma were measured weekly and 5-FU clearance was calculated. Both before and after the addition of OXA, the 5-FU dose was individually adjusted according to the pharmacokinetic follow-up (target steady-state plasma concentrations 2.5-3 mg/l).

RESULTS AND DISCUSSION:

A total of 122 OXA-containing infusions and 338 5-FU plus FA infusions were given and the median number of infusions per patient was 4 (2-9) and 10 (5-28), respectively. 5-FU plasma clearance was significantly decreased on days 8 and 15 when compared with the value on day 1 and with the values before OXA introduction using a direct paired comparison (2.36 and 2.31 l/min, respectively, vs 3.12 and 3.05 l/min; P<10(-5)). Of 25 evaluable patients, 6 had an objective response after the introduction of OXA (24% objective response rate, 95% confidence interval 9.4-45%).

CONCLUSION:

OXA reduces 5-FU plasma clearance for 15 days. This may be a factor in the synergy between the two drugs. It is not linked to dihydropyrimidine dehydrogenase inhibition. Implications for drug schedules in clinical practice are discussed.

PMID:
11935216
DOI:
10.1007/s00280-001-0406-2
[Indexed for MEDLINE]

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