We have shown previously that a reduction from the conventional dose of tamoxifen is associated with a comparable modulation of circulating biomarkers, including insulin-like growth factor-I and cholesterol. In the present study, we have correlated serum tamoxifen elimination with biomarker recovery in healthy subjects completing a 5-year intervention period. Tamoxifen, N-desmethyltamoxifen, and biomarker levels were measured at 0 (baseline), 2, 4, and 6 weeks after completion of treatment in 23 healthy postmenopausal women allocated to tamoxifen 20 mg/day and in 6 women allocated to placebo. Mean (±SD) serum tamoxifen and N-desmethyltamoxifen concentrations were, respectively, 141 ± 50 and 226 ± 77 ng/ml at baseline, 36 ± 19 and 99 ± 46 at 2 weeks, 20 ± 15 and 61 ± 37 at 4 weeks, and 12 ± 9 and 36 ± 26 at 6 weeks. Serum tamoxifen and N-desmethyltamoxifen half-lives were 9 and 13 days, respectively. Body mass index was associated positively with drug's serum half-life. Compared with baseline values, the percentage increase in total cholesterol, low-density lipoprotein cholesterol, and insulin-like growth factor-I 4 weeks after treatment completion was 5, 9, and 14%, respectively. No change during the 6-week period was observed in the placebo arm. Our findings indicate that the biomarker recovery is slower than serum tamoxifen elimination, suggesting that low tamoxifen concentrations may still exert a biological effect. In addition, the prolonged half-life of tamoxifen and metabolite provides the rationale for a weekly administration of the drug in a preventive context. However, the clinical implications of our findings remain to be defined.

Correlation between tamoxifen elimination and biomarker recovery in a primary prevention trial

BAGLIETTO, LAURA;
2001-01-01

Abstract

We have shown previously that a reduction from the conventional dose of tamoxifen is associated with a comparable modulation of circulating biomarkers, including insulin-like growth factor-I and cholesterol. In the present study, we have correlated serum tamoxifen elimination with biomarker recovery in healthy subjects completing a 5-year intervention period. Tamoxifen, N-desmethyltamoxifen, and biomarker levels were measured at 0 (baseline), 2, 4, and 6 weeks after completion of treatment in 23 healthy postmenopausal women allocated to tamoxifen 20 mg/day and in 6 women allocated to placebo. Mean (±SD) serum tamoxifen and N-desmethyltamoxifen concentrations were, respectively, 141 ± 50 and 226 ± 77 ng/ml at baseline, 36 ± 19 and 99 ± 46 at 2 weeks, 20 ± 15 and 61 ± 37 at 4 weeks, and 12 ± 9 and 36 ± 26 at 6 weeks. Serum tamoxifen and N-desmethyltamoxifen half-lives were 9 and 13 days, respectively. Body mass index was associated positively with drug's serum half-life. Compared with baseline values, the percentage increase in total cholesterol, low-density lipoprotein cholesterol, and insulin-like growth factor-I 4 weeks after treatment completion was 5, 9, and 14%, respectively. No change during the 6-week period was observed in the placebo arm. Our findings indicate that the biomarker recovery is slower than serum tamoxifen elimination, suggesting that low tamoxifen concentrations may still exert a biological effect. In addition, the prolonged half-life of tamoxifen and metabolite provides the rationale for a weekly administration of the drug in a preventive context. However, the clinical implications of our findings remain to be defined.
2001
Guerrieri Gonzaga, A.; Baglietto, Laura; Johansson, H.; Bonanni, B.; Robertson, C.; Sandri, M. T.; Canigiula, L.; Lampreda, C.; Diani, S.; Lien, E. A.; Decensi, A.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/816412
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 33
  • ???jsp.display-item.citation.isi??? ND
social impact