CORRELATION BETWEEN PLASMA TAMOXIFEN CONCENTRATION AND TUMOR RESPONSE IN PATIENTS WITH BREAST CANCER: AT NEOADJUVANT TREATMENT WITH TAMOXIFEN
Objective: to determine a possible correlation between the tumor response in patients suffering from breast cancer, initially treated with tamoxifen, and plasma concentration of this drug.
Methods: we studied 27 elderly patients (age range: 62 to 82 y) with advanced breast carcinoma who were treated with a daily dose of 20 mg of oral tamoxifen, for 3 mo. Responders were followed-up for 19 mo, and nonresponders for 21 mo. We measured plasma tamoxifen citrate levels in order to determine their possible correlation with objective remission of the disease.
Results: the correlation was found to be significant among responders (37%), whose median plasma tamoxifen level was 187.40ng. ml-1, when comparing to non-responders, whose median plasma tamoxifen level was 99.52ng. ml-1. The frequency distribution of patients in both groups with concentration of tamoxifen lower and higher than 182.60ng. ml-1 was significant (fisher's test p-value<0,0011).
Conclusion: considering the results herein, we suggest that patients whose plasma tamoxifen levels reach 182.60ng. ml-1 after 3 mo of treatment, with no tumor response, may not benefit from this treatment, and an alternative therapy should be regarded.
2. Sato M, Glasebrook AL, Bryant HU. Raloxifene: a selective estrogen receptor modulator. J Bon Min Metab 1994;12:9-20.
3. Reddel LL, Sutherland RL. Tamoxifen stimulation of human breast cancer cell proliferation in vitro. A possible model for tamoxifen tumour fare. Eur J Cancer Clin Oncol 1984;11:1419-24.
4. Bonadonna G. Cancer of the breast. In: Bonadonna G, Robustelli Della Cuna G. Handbook of Medical Oncology. Milan: Masson; 1988. p. 407-32.
5. Bonadonna G, Bernardo G, Luca G, Robustelli Della Cuna G. Pharmacology, clinical toxicity, dosage and general indications of growth inhibiting compounds. Cancer of the breast. In: Bonadonna G, Robustelli Della Cuna J. Handbook of Medical Oncology. Milan: Masson; 1988. p. 335-77.
6. Iacobelli S, Lippman ME, Robustelli Della Cuna G. The role of tamoxifen in breast cancer. New York: Raven Press; 1982.
7. Sharma P, Kumar P, Sharma R, Dikshit DK. Selective estrogen receptor modulators; role of side chain in activity modulation. Asian J Pharm Clin Res 2014;7:272-4.
8. Binkhorst L, Mathijssen RH, Jager A, van Gelder T. Individualization of tamoxifen therapy: much more than just CYP2D6 genotyping. Cancer Treat Rev 2015;41:289-99.
9. Ahmad A, Ali SM, Ahmad MU, Sheikh S, Ahmad I. Orally administered endoxifen is a new therapeutic agent for breast cancer. Breast Cancer Res Treat 2010;122:579-84.
10. Howell A, De Friend D, Anderson E. Mechanisms of response and resistance to endocrine therapy for breast cancer and the development of new treatments. Endocr Relat Cancer 1993;43:5-21.
11. Westerberg H, Nordenskjould B, Schriver A, Notter G. Anti-oestrogen therapy of advanced mammary carcinoma. Acta Radiol Ther Phys Biol 1976;15:513-8.
12. Mouridsen H, Palshof T, Patterson J, Battersby I. Tamoxifen in advanced breast cancer. Cancer Treat Rev 1978;5:131-41.
13. Manni A, Bahaâ€™uddin MA. Tamoxifen-induced remission in breast cancer by escalating the dose to 40 mg daily after progression on 20-20 mg daily: a case\report and review of the literature. Cancer 1981;48:875-8.
14. Hsu SM, Raine L, Fanger H. Self sandwich method. An improved immunoperoxidase technic for the detection of small amounts of antigens. Am J Clin Pathol 1980;4:32-74.
15. Meeting on the standardisation of reporting results of cancer treatment: In: WHO Handbook for Reporting Results of Cancer Treatment. World Health Organization. Geneva; 1979.
16. Farante G, Costa A, Arrighi A, Rancati A, Cuneo J, Borhi L, et al. Nueva estrategia frente al cancer de mama: la quimioprevenciÃ³n com tamoxifen. Tumor 1994;7:33-90.
17. Early Breast Cancer Trialistsâ€™ Collaborative Group: Systemic treatment of early breast cancer by hormonal, cytotoxic or immune therapy. Lancet 1992;4:1-15.
18. Qureshi SS, Gupta JK, Shah K, Upmanyu N. Prevalence and risk factor of polycystic ovarian syndrome. Asian J Pharm Clin Res 2016;9:23-5.
19. Maurya H, Kumar T. A review on comprehensive overview in the management of nephrotic disorders. J Crit Rev 2016;3:34-43.
20. Peyrade F, Frenay M, Etienne MC, Ruch F, Guillemare C, FranÃ³is E, et al. Age-related difference in tamoxifen disposition. Clin Pharmacol Ther 1996;59:401-10.
21. Andrade JM, Marana HRC, Filho JMS, Murta EFC, Velludo MAL, Bighetti S. Indicadores clÃnicos com valor prognÃ³stico no tratamento neo-adjuvante de carcinoma avanÃ§ado de mama. Acta Oncol Bras 1994;14:180-6.
22. Jordan VC. Metabolites of tamoxifen in animals and man: identification, pharmacology, and significance. Brest Cancer Res Treat 1982;2:123-8.
23. Meriel P, Golder M, Elizabeth A, Phillips D, Fahmy R, Preece PE, et al. Plasma hormones in patients with advanced breast cancer treated with tamoxifen. Eur J Cancer 1976;12:719-23.
24. Lerner HJ, Band PR, Israel I, Leung BD. Phase II study of tamoxifen: report of 74 patients with stage IV breast cancer. Cancer Treat Reprod 1976;60:1431-5.
25. Stoll BA. Prognostic indices in breast cancer. In: Stoll BA. Pointers to Cancer Prognosis. Martinius Nijhoff: Dordrecht; 1987. p. 195.
26. Ward HWC. Anti oestrogen therapy for breast cancer: a trial of tamoxifen at two dose levels. Br Med J 1973;1:13-4.
27. Ward HWC, Arthur K, Banks AJ, Bond WH, Brown I, Freeman WE, et al. Anti oestrogen therapy for breast cancer-a report on 300 patients treated with tamoxifen. Clin Oncol 1978;4:11-7.
28. Adam HK. Pharmacokinetic studies with nolvadex. Rev Endocr Relat Cancer 1981;9:131-43.
29. Wada T, Koyama H, Terasawa T, Hongo E. Tamoxifen: its pharmacokinetics in blood concentration in human blood and how it changes. Jpn Basic Pharmacol Ther 1980;8:49-56.
30. Patterson JS. Clinical aspects and development of antiestrogen therapy: a review of the endocrine effects of tamoxifen in animals and man. J Endocrinol 1981;89:67-75.
31. Ducharme J, Fried K, Shenouda G, Leyland-Jones B, Wainer IW. Tamoxifen metabolic patterns within a glioma patient population treated with high-dose tamoxifen. Br J Clin Pharmacol 1997;43:189-93.
32. Walko CM, McLeod H. Use of CYP2D6 genotyping in practice: tamoxifen dose adjustment. Pharmacogenomics 2012;13: 691-7.
33. Ruddy KJ, Desantis SD, Gelman RS, Wu AH, Punglia RS, Mayer EL, et al. Personalized medicine in breast cancer: tamoxifen, endoxifen, and CYP2D6 in clinical practice. Breast Cancer Res Treat 2013;141:421-7.
34. Schiavon G, Smith IE. Endocrine therapy for advanced/ metastatic breast cancer. Hematol Oncol Clin North Am 2013;27:715â€“36.
35. Dickschen K, Eissing T, Murdter T, Schwab M, Willmann S, Hempel G. Concomitant use of tamoxifen and endoxifen in postmenopausal early breast cancer: prediction of plasma levels by physiologically-based pharmacokinetic modeling. Springerplus 2014;3:285.