Abstract | PURPOSE: PATIENTS AND METHODS: RESULTS: Patients with cyclophosphamide plasma exposures above the median (implying slower metabolic activation) had a shorter survival than those below the median (1.8 v 3.8 years, respectively; P = .042). Patients having a variant genotype of cytochrome P450 3A4 displayed higher blood concentrations of parent (inactive) cyclophosphamide with the second and third doses (P = .024 and .028, respectively) in addition to slower cyclophosphamide activation over the three doses (P = .031). Median survival for these patients was 1.3 years compared with 2.7 years for those without the variant (P = .043). Similar results were observed for patients carrying a genetic variant of P450 3A5. Median survival for patients with deletions of glutathione-S-transferase M1 gene was 3.5 v 1.5 years for patients with one or both copies (P = .041). Patients with a polymorphism in a gene regulating metallothionein had lower platinum concentrations and shorter survival (P = .033). CONCLUSION: These data suggest that pretreatment evaluation of drug metabolism genes may explain some interindividual differences in both anticancer drug pharmacokinetics and response. The correlations found here may have implications for other commonly used anticancer drugs.
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Authors | William P Petros, Penelope J Hopkins, Susan Spruill, Gloria Broadwater, James J Vredenburgh, O Michael Colvin, William P Peters, Roy B Jones, Jeff Hall, Jeffrey R Marks |
Journal | Journal of clinical oncology : official journal of the American Society of Clinical Oncology
(J Clin Oncol)
Vol. 23
Issue 25
Pg. 6117-25
(Sep 01 2005)
ISSN: 0732-183X [Print] United States |
PMID | 16087946
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Cyclophosphamide
- Cisplatin
- Carmustine
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Topics |
- Adult
- Antineoplastic Combined Chemotherapy Protocols
(pharmacokinetics, therapeutic use)
- Breast Neoplasms
(drug therapy, genetics, pathology)
- Carmustine
(administration & dosage, pharmacokinetics)
- Cisplatin
(administration & dosage, pharmacokinetics)
- Cyclophosphamide
(administration & dosage, pharmacokinetics)
- Female
- Genotype
- Humans
- Middle Aged
- Polymorphism, Genetic
- Prognosis
- Survival Analysis
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