Abstract | PURPOSE: PATIENTS AND METHODS: One hundred eighty-five unselected consecutive cancer patients were included. The population consisted of 152 men (mean age, 62.1 years; range, 35 to 90) and 33 women (mean age, 59.2 years; range, 36 to 77). Sixty-eight were head and neck patients treated by a 5-day continuous infusion of fluorouracil (FU; starting dose, 1 g/m2/d, with dose adaptation based on pharmacokinetics) for which DPD activity was measured 2 to 3 days before FU administration (94 cycles analyzed). PMNC-DPD activity was measured by a radio-enzymatic assay using carbon-14-FU. RESULTS: DPD activity in the entire population showed a unimodal distribution, which globally fits a gaussian distribution. Mean and median DPD activity values were 0.222 and 0.211 nmol/min/mg protein, respectively (range, 0.065 to 0.559). No total DPD deficiency was found. Multifactor analysis of variance showed that liver function ( biologic evaluation) and age did not influence DPD activity, but that DPD activity was, on average, 15% lower in women (0.194 nmol/min/mg protein) than in men (0.228 nmol/min/mg protein) (P = .03). No difference was demonstrated between premenopausal and postmenopausal women. In patients treated with FU, the risk of developing side effects was not linked to pretreatment DPD activity. FU-related toxicity was linked to FU systemic exposure. The correlation between pretreatment DPD activity and FU systemic clearance (CI) was weak (n = 90, linear regression r = .31, P = .002). Pretreatment DPD activity in patients who required a dose reduction was not significantly different from DPD activity in patients who did not require dose modification. CONCLUSION: From the present study, it appears that total DPD deficiency is a rare event. Although pretreatment DPD activity cannot be a useful indicator for improving FU dose adaptation strategy, the identification of severe DPD deficiency (< 0.100 nmol/min/mg protein) could lead to starting the treatment with a markedly reduced FU dose or even to using an alternative chemotherapy regimen.
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Authors | M C Etienne, J L Lagrange, O Dassonville, R Fleming, A Thyss, N Renée, M Schneider, F Demard, G Milano |
Journal | Journal of clinical oncology : official journal of the American Society of Clinical Oncology
(J Clin Oncol)
Vol. 12
Issue 11
Pg. 2248-53
(Nov 1994)
ISSN: 0732-183X [Print] United States |
PMID | 7964939
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Oxidoreductases
- Dihydrouracil Dehydrogenase (NADP)
- Fluorouracil
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Topics |
- Adult
- Aged
- Aged, 80 and over
- Dihydrouracil Dehydrogenase (NADP)
- Female
- Fluorouracil
(pharmacokinetics, therapeutic use)
- Head and Neck Neoplasms
(drug therapy, enzymology)
- Humans
- Leukocytes, Mononuclear
(enzymology)
- Liver
(enzymology)
- Male
- Middle Aged
- Normal Distribution
- Oxidoreductases
(deficiency, metabolism)
- Prospective Studies
- Sex Factors
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