CORRELATION BETWEEN PLASMA TAMOXIFEN CONCENTRATION AND TUMOR RESPONSE IN PATIENTS WITH BREAST CANCER: AT NEOADJUVANT TREATMENT WITH TAMOXIFEN
DOI:
https://doi.org/10.22159/ijpps.2017v9i9.19460Keywords:
Breast cancer, Tumor response, Plasma tamoxifen, NeoadjuvantAbstract
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.
Downloads
References
Beatson GT. On the treatment of inoperable cases of carcinoma of the mamma. Suggestions for a new method of treatment with illustrative cases. Lancet 1986;2:104-7.
Sato M, Glasebrook AL, Bryant HU. Raloxifene: a selective estrogen receptor modulator. J Bon Min Metab 1994;12:9-20.
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.
Bonadonna G. Cancer of the breast. In: Bonadonna G, Robustelli Della Cuna G. Handbook of Medical Oncology. Milan: Masson; 1988. p. 407-32.
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.
Iacobelli S, Lippman ME, Robustelli Della Cuna G. The role of tamoxifen in breast cancer. New York: Raven Press; 1982.
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.
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.
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.
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.
Westerberg H, Nordenskjould B, Schriver A, Notter G. Anti-oestrogen therapy of advanced mammary carcinoma. Acta Radiol Ther Phys Biol 1976;15:513-8.
Mouridsen H, Palshof T, Patterson J, Battersby I. Tamoxifen in advanced breast cancer. Cancer Treat Rev 1978;5:131-41.
Manni A, Baha’uddin MA. Tamoxifen-induced remission in breast cancer by escalating the dose to 40 mg daily after progression on 20-20 mg daily: a casereport and review of the literature. Cancer 1981;48:875-8.
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.
Meeting on the standardisation of reporting results of cancer treatment: In: WHO Handbook for Reporting Results of Cancer Treatment. World Health Organization. Geneva; 1979.
Farante G, Costa A, Arrighi A, Rancati A, Cuneo J, Borhi L, et al. Nueva estrategia frente al cancer de mama: la quimioprevención com tamoxifen. Tumor 1994;7:33-90.
Early Breast Cancer Trialists’ Collaborative Group: Systemic treatment of early breast cancer by hormonal, cytotoxic or immune therapy. Lancet 1992;4:1-15.
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.
Maurya H, Kumar T. A review on comprehensive overview in the management of nephrotic disorders. J Crit Rev 2016;3:34-43.
Peyrade F, Frenay M, Etienne MC, Ruch F, Guillemare C, Franóis E, et al. Age-related difference in tamoxifen disposition. Clin Pharmacol Ther 1996;59:401-10.
Andrade JM, Marana HRC, Filho JMS, Murta EFC, Velludo MAL, Bighetti S. Indicadores clÃnicos com valor prognóstico no tratamento neo-adjuvante de carcinoma avançado de mama. Acta Oncol Bras 1994;14:180-6.
Jordan VC. Metabolites of tamoxifen in animals and man: identification, pharmacology, and significance. Brest Cancer Res Treat 1982;2:123-8.
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.
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.
Stoll BA. Prognostic indices in breast cancer. In: Stoll BA. Pointers to Cancer Prognosis. Martinius Nijhoff: Dordrecht; 1987. p. 195.
Ward HWC. Anti oestrogen therapy for breast cancer: a trial of tamoxifen at two dose levels. Br Med J 1973;1:13-4.
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.
Adam HK. Pharmacokinetic studies with nolvadex. Rev Endocr Relat Cancer 1981;9:131-43.
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.
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.
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.
Walko CM, McLeod H. Use of CYP2D6 genotyping in practice: tamoxifen dose adjustment. Pharmacogenomics 2012;13: 691-7.
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.
Schiavon G, Smith IE. Endocrine therapy for advanced/ metastatic breast cancer. Hematol Oncol Clin North Am 2013;27:715–36.
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.
Published
How to Cite
Issue
Section
