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Clinical Pharmacokinetics of Endocrine Agents Used in Advanced Breast Cancer

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Summary

Endocrine therapy is important in the treatment of advanced breast cancer. The prototype antiestrogen tamoxifen and the prototype aromatase inhibitor aminoglutethimide have been in clinical use for more than 2 decades, as have synthetic progestin derivatives. Currently, several novel antiestrogens and aromatase inhibitors are used to treat breast cancer. This paper reviews the present knowledge of the clinical pharmacokinetics of these drugs. Drug monitoring in plasma and other body fluids has been improved over recent years by the introduction of sensitive and specific high performance liquid chromatography and gas chromatography-mass spectrometry methods. However, we still lack information on such basic pharmacokinetic parameters as the bioavailability of several of these drugs. It is important to study not only plasma but also tissue drug concentrations.

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References

  • Abe O. Japanese early phase II study of droloxifene in the treatment of advanced breast cancer: preliminary dose-finding study. American Journal of Clinical Oncology 14 (Suppl.): 40–45, 1991

    Article  Google Scholar 

  • Aboul-Enein HY, Islam MR. Direct liquid chromatographic resolution of racemic aminoglutethimide and its acetyled metabolite using a chiral alfa 1-acid glycoprotein column. Journal of Chromatographic Science 26: 616–619, 1988

    PubMed  CAS  Google Scholar 

  • Ackermann R, Kaiser G. Determination of the new aromatase inhibitor CGS 16949 in biological fluids by capillary gas chromatography/mass spectrometry. Biomedical and Environmental Mass Spectrometry 18: 558–562, 1989

    Article  PubMed  CAS  Google Scholar 

  • Adam AM, Bradbrook ID, Rogers HJ. High-perfomance liquid chromatographic assay for simultaneous estimation of aminoglutethimide and acethylamidoglutethimide in biological fluids. Cancer Chemotherapy and Pharmacology 15: 176–178, 1985

    Article  PubMed  CAS  Google Scholar 

  • Adam AM, Rogers HJ, Amiel SA, Rubens RD. The effect of acetylator phenotype on the disposition of aminoglutethimide. British Journal of Clinical Pharmacology 18: 495–505, 1984

    Article  PubMed  CAS  Google Scholar 

  • Adam, HK. A review of the pharmacokinetics and metabolism of ‘Nolvadex’ (tamoxifen). In Sutherland (Ed.) Non-steroidal antiestrogens: molecular pharmacology and antitumour activity, pp. 59–74, Academic Press, 1981

    Google Scholar 

  • Adam HK, Barker Y, Hutchinson FG, Milsted RAV, Moore RH, et al. Zoladex: a one-month duration LH-RH agonist. Symposium on Disposition and Delivery of Peptide Drugs, Leiden, September 5–6, 1987. Abstract no. 8964. Pharmaceutisch Weekblad — Scientific Edition 10, 57, 1988

    Google Scholar 

  • Adam HK, Douglas EJ, Kemp JV. The metabolism of tamoxifen in humans. Biochemical Pharmacology 27: 145–147, 1979

    Article  Google Scholar 

  • Adam HK, Gay MA, Moore RH. Measurement of tamoxifen in serum by thin-layer densitometry. Journal of Endocrinology 84: 35–42, 1980a

    Article  PubMed  CAS  Google Scholar 

  • Adam HK, Patterson JS, Kemp JV. Studies on the metabolism and pharmacokinetics of tamoxifen in normal volunteers. Cancer Treatment Reports 64: 761–764, 1980b

    PubMed  CAS  Google Scholar 

  • Adjei A, Garren J. Pulmonary delivery of peptide drugs: effect of particle size on bioavailability of leuprolide acetate in healthy male volunteers. Pharmaceutical Research 7: 565–569, 1990

    Article  PubMed  CAS  Google Scholar 

  • Adlercreutz H, Eriksen PB, Christensen MS. Plasma concentration of megestrol acetate and medroxyprogesterone acetate after single oral administration to healthy subjects. Journal of Pharmaceutical and Biomedical Analysis 1: 153–162, 1983

    Article  PubMed  CAS  Google Scholar 

  • Adlercreutz H, Harkonen M. Enzymatic assay of medroxyprogesterone acetate in plasma. Journal of Steroid Biochemistry 13: 507–515, 1980

    Article  PubMed  CAS  Google Scholar 

  • Adlercreutz H, Martin F, Pulkkinen M, Dencker H, Rimer U, et al. Intestinal metabolism of estrogens. Journal of Clinical Endocrinology and Metabolism 43: 497–505, 1976

    Article  PubMed  CAS  Google Scholar 

  • Adlercreutz H, Nieminen U, Ervast HS. A mass fragmentographic method for the determination of megestrol acetate in plasma and its application to studies on the plasma levels after administration of the progestin to patients with carcinoma corporis uteri. Journal of Steroid Biochemistry 5: 619–626, 1974

    Article  Google Scholar 

  • Ahlemann LM, Staab H-J, Loser R, Seibel K, Huber H-J. Inhibition of growth of human cancer by intermittent exposure to the antiestrogen droloxifene. Tumordiagnostik und Therapie 9: 41–46, 1988

    Google Scholar 

  • Ahmad B, Nicholls PJ, Smith HJ, Pourgholami MH. Tissue distribution of aminoglutethimide in the female rat. British Journal of Pharmacology 93: 215, 1988

    Article  Google Scholar 

  • Ahmann FR, Citrin DL, Guinan P, Jordan VC, Kreis W, et al. Zoladex: a monthly depot LH-RH analog for prostate cancer. Proceedings of the Annual Meeting of the American Society for Clinical Oncology, Abstract no. A412, 1986

  • Alexieva-Figusch J, Blankenstein MA, Hop WCJ, Klijn JGM, Lamberts SWJ, et al. Treatment of metastatic breast cancer patients with different dosages of megestrol acetate; dose relations, metabolic and endocrine efffects. European Journal of Cancer and Clinical Oncology 20: 33–40, 1984

    Article  CAS  Google Scholar 

  • Allegra JC, Kiefer SM. Mechanism of action of progestational agents. Seminars in Oncology 12: 3–5, 1985

    PubMed  CAS  Google Scholar 

  • Alonso-Munoz MC, Ojeda Gonzalez MB, Beltran-Fabregat M, Dorca-Ribugent J, Lopez-Lopez L, et al. Randomized trial of tamoxifen versus aminoglutethimide and versus combined tamoxifen and aminoglutethimide in advanced postmenopausal breast cancer. Oncology 45: 350–353, 1988

    Article  PubMed  CAS  Google Scholar 

  • Antila M, Valavaara R, Kivinen S, Maenpaa J. Pharmacokinetics of toremifene. Journal of Steroid Biochemistry 36: 249–252, 1990

    Article  Google Scholar 

  • Appelgren L-E, Brittebo E, Carlstrøm K, Theve NO, Wilking N. Distribution and metabolism studies of 14C-labelled aminoglutethimide in mice. Abstract. 2nd Scandinavian Breast Cancer Symposium, Bergen, Norway, May 23–24, 1985

  • Ayub M, Levell MJ. Structure-activity relationships of the inhibition of human placental aromatase by imidazole drugs including ketoconazole. Journal of Steroid Biochemistry 31: 65–72, 1988

    Article  PubMed  CAS  Google Scholar 

  • Babcock JC, Gutsell ES, Herr ME, Hogg JA, Stucki JC, et al. 6-α-Methyl-17-a-hydroxyprogesterone 17-acylates: a new class of potent progestins. Journal of the American Chemical Society 80: 2904–2905, 1958

    Article  CAS  Google Scholar 

  • Banting L, Nicholls PJ, Shaw MA, Smith HJ. Recent developments in aromatase inhibition as a potential treatment for oestrogen-dependent breast cancer. Progress in Medical Chemistry 26: 253–298, 1989

    Article  CAS  Google Scholar 

  • Barany E, Morsing P, Muller W, Stallberg G, Stenhagen E. Inhibition of estrogen-induced proliferation of the vaginal epithelium in the rat by topical application of certain 4,4′-hy-droxydiphenylalkanes and related compounds. Acta Societatis Medicorum Upsaliensis 72: 68–75, 1955

    Google Scholar 

  • Barron JL, Millar RP, Searle DI. Metabolic clearance and plasma half-disappearance time of D-Trp6 and exogenous luteinizing hormone-releasing hormone. Journal of Clinical Endocrinology and Metabolism 54: 1169–1173, 1982

    Article  PubMed  CAS  Google Scholar 

  • Beex L, Burghouts J, van Turnhout J, Breed W, Hillen H, et al. Oral versus i.m. administration of high-dose medroxyprogesterone acetate in pretreated patients with advanced breast cancer. Cancer Treatment Reports 71: 1151–1156, 1987

    PubMed  CAS  Google Scholar 

  • Bellmunt J, Sole LA. European early phase II dose finding study of droloxifene in advanced breast cancer. American Journal of Clinical Oncology 14 (Suppl. 2): s36–s39, 1991

    Article  PubMed  Google Scholar 

  • Bennet HPJ, McMartin C. Peptide hormones and their analogues: distribution, clearance from the circulation, and inactivation in vivo. Pharmacological Reviews 30: 247–292, 1979

    Google Scholar 

  • Beretta KR, Hoeffken K, Kvinnsland S, Trunet P, Chaudri HA, et al. CGS 16949A, a new aromatase inhibitor in the treatment of breast cancer — a phase I study. Annals of Oncology 1: 421–426, 1990

    PubMed  CAS  Google Scholar 

  • Blom JH, Hirdes WH, Schrør FH, de Jong FH, Kwekkeboom DJ, et al. Pharmacokinetics and endocrine effects of the LHRH analogue buserelin after subcutaneous implantation of a slow release preparation in prostatic cancer patients. Urological Research 17: 43–46, 1989

    Article  PubMed  CAS  Google Scholar 

  • Blumenschein GR. The role of progestins in the treatment of breast cancer. Seminars in Oncology 10: 7–10, 1983

    PubMed  CAS  Google Scholar 

  • Borgna J-L, Rochefort H. Hydroxylated metabolites of tamoxifen are formed in vivo and bound to estrogen receptor in target tissues. Journal of Biological Chemistry 256: 859–868, 1981

    PubMed  CAS  Google Scholar 

  • Brandes LJ, Bogdanovic RP. New evidence that the antiestrogen binding site may be a novel growth-promoting histamine receptor (?H3) which mediates the antiestrogenic and antiproliferative effects of tamoxifen. Biochemical and Biophysical Research Communications 134: 601–608, 1986

    Article  PubMed  CAS  Google Scholar 

  • Brodie AMH, Garrett WM, Hendrickson JR, Tsai-Morris C-H, Marcotte PA, et al. Inactivation of aromatase in vitro by 4-hydroxy-4-androstene-3, 17-dione and 4-acetoxy-4-androstene-3,17-dione and sustained effects in vivo. Steroids 38: 693–701, 1981a

    Article  PubMed  CAS  Google Scholar 

  • Brodie AMH, Longcope C. Inhibition of peripheral aromatization by aromatase inhibitors, 4-hydroxy- and 4-acetoxy-androstene-3,17-dione. Endocrinology 106: 19–21, 1980

    Article  PubMed  CAS  Google Scholar 

  • Brodie AMH, Romanoff LP, Williams KIH. Metabolism of the aromatase inhibitor 4-hydroxy-4-androstene-3,17-dione by male rhesus monkeys. Journal of Steroid Biochemistry 14: 693–696, 1981b

    Article  PubMed  CAS  Google Scholar 

  • Brodie AMH, Son C, King DA, Meyer KM, Inkster SE. Lack of evidence for aromatase in human prostatic tissues: effects of 4-hydroxyandrostenedione and other inhibitors on androgen metabolism. Cancer Research 49: 6551–6555, 1989

    PubMed  CAS  Google Scholar 

  • Brodie AMH, Wing L-Y, Goss P, Dowsett M, Coombes RC. Aromatase inhibitors and the treatment of breast cancer. Journal of Steroid Biochemistry 24: 91–97, 1986

    Article  PubMed  CAS  Google Scholar 

  • Brogden RN, Buckley MMT, Ward A. Buserelin: a review of its pharmacodynamic and pharmacokinetic properties, and clinical profile. Drugs 39: 399–437, 1990

    Article  PubMed  CAS  Google Scholar 

  • Brown RR, Bain R, Jordan VC. Determination of tamoxifen and metabolites in human serum by high-performance liquid chromatography with post-column fluorescence activation. Journal of Chromatography 272: 351–358, 1983

    Article  PubMed  CAS  Google Scholar 

  • Butzow R, Huntaniemi I, Clayton R, Wahlstrom T, Andersson LC, et al. Cultured mammary carcinoma cells contain gonadotropin-releasing hormonelike immunoreactivity, GnRH binding sites and chorionic gonadotropin. International Journal of Cancer 39: 498–501, 1987

    Article  CAS  Google Scholar 

  • Caleffi M, Fentiman IS, Clark GM, Wang DY, Needham J, et al. Effect of tamoxifen on estrogen binding, lipid and lipoprotein concentrations and blood clotting parameters in premenopausal women with breast pain. Journal of Endocrinology 119: 335–339, 1988

    Article  PubMed  CAS  Google Scholar 

  • Camaggi CM. High-performance liquid chromatographic analysis of tamoxifen and major metabolites in human plasma. Journal of Chromatography 275: 436–442, 1983

    Article  PubMed  CAS  Google Scholar 

  • Camaggi CM, Strocchi E, Canova N, Costani B, Pannuti F. Medroxyprogesterone acetate (MAP) and tamoxifen (TMX) plasma levels after simultaneous treatment with ‘low’ TMX and ‘high’ MAP doses. Cancer Chemotherapy and Pharmacology 14: 229–331, 1985b

    PubMed  CAS  Google Scholar 

  • Camaggi CM, Strocchi E, Costanti B, Beghelli P, Ferrari P, et al. Medroxyprogesterone acetate bioavailability after high-dose intraperitoneal administration in advanced cancer. Cancer Chemotherapy and Pharmacology 14: 232–234, 1985c

    PubMed  CAS  Google Scholar 

  • Camaggi CM, Strocchi E, Pannuti F. Tamoxifen pharmacokinetics in advanced breast cancer patients.In Pannúti (Ed.) Antioestrogens in oncology: past, present and prospects, pp. 90–97, Amsterdam, Excerpta Medica, 1985a

    Google Scholar 

  • Canney PA, Priestman TJ, Griffiths T, Latief TN, Mould JJ, et al. Randomized trial comparing aminoglutethimide with high-dose medroxyprogesterone acetate in therapy for advanced breast carcinoma. Journal of the National Cancer Institute 80: 1147–1151, 1988

    Article  PubMed  CAS  Google Scholar 

  • Cash R, Brough AJ, Cohen MNP, Satoh PS. Aminoglutethimide (Elipten-Ciba) is an inhibitor of adrenal steroidogenesis: mechanism of action and therapeutic trial. Journal of Clinical Endocrinology 27: 1239–1248, 1967

    Article  CAS  Google Scholar 

  • Chan RL, Chaplin MD. Plasma binding of LHRH and nafarelin acetate, a highly potent LHRH agonist. Biochemical and Biophysical Research Communications 127: 673–679, 1985

    Article  PubMed  CAS  Google Scholar 

  • Chan RL, Henzl MR, LePage ME, LaFargue J, Nerenberg CA, et al. Absorption and metabolism of nafarelin, a potent agonist of gonadotropin-releasing hormone. Clinical Pharmacology and Therapeutics 44: 275–282, 1988

    Article  PubMed  CAS  Google Scholar 

  • Chien YW. Long acting parenteral drug formulation. Journal of Parenteral Science and Technology 36: 106–139, 1981

    Google Scholar 

  • Chrisp P, Goa KL. Nafarelin: a review of its pharmacodynamic and pharmacokinetic properties, and clinical potential in sex hormone-related conditions. Drugs 39: 523–551, 1990

    Article  PubMed  CAS  Google Scholar 

  • Chrisp P, Goa KL. Goserelin: a review of its pharmacodynamic and pharmacokinetic properties, and clinical use in sex hormone-related conditions. Drugs 41: 254–288, 1991

    Article  PubMed  CAS  Google Scholar 

  • Ciocca DR, Puy LA, Fasoli LC, Tello O, Azhar JC, et al. Corticotropin-releasing hormone, luteinizing hormone-releasing hormone, and somatostatin-like immunoreactivities in biopsies from breast cancer patients. Breast Cancer Research and Treatment 15: 175–184, 1990

    Article  PubMed  CAS  Google Scholar 

  • Clark AG, Fisher LJ, Millburn P, Smith RL, Williams RT. The role of gut flora in the enterohepatic circulation of stilbestrol in the rat. Biochemical Journal 112: 17–18, 1969

    Google Scholar 

  • Clayton RN, Bailey LC, Cottam J, Arkell D, Perren TJ, et al. A radioimmunoassay for GnRH agonist analogue in serum of patients with prostate cancer treated with D-Ser (tBu)6 AZA Gly10 GnRH. Clinical Endocrinology 22: 453–462, 1985

    Article  PubMed  CAS  Google Scholar 

  • Clayton RN, Catt KJ. Gonadotropin-releasing hormone receptors: characterization, physiological regulation and relationship to reproductive function. Endocrine Reviews 2: 186–209, 1981

    Article  PubMed  CAS  Google Scholar 

  • Clayton RN, Shakespear RA, Duncan JA, Marshall JC. LHRH inactivation by purified pituitary plasma membranes: effects on receptor binding studies. Endocrinology 104: 1484–1489, 1979

    Article  PubMed  CAS  Google Scholar 

  • Coombes RC. 4-Hydroxyandrostenedione treatment for advanced breast cancer. 15th International Cancer Congress, Hamburg, August 16–22, y1990

  • Coombes RC, Foster AB, Harland SJ, Jarman M, Nice EC. Polymorphically acetylated aminoglutethimide in humans. British Journal of Cancer 46: 340–345, 1982

    Article  PubMed  CAS  Google Scholar 

  • Coombes RC, Goss P, Dowsett M, Gazet J-C, Brodie A. 4-Hydroxyandrostenedione in treatment of postmenopausal patients with advanced breast cancer. Lancet 2: 1237–1239, 1984

    Article  PubMed  CAS  Google Scholar 

  • Coombes RC, Jarman M, Harland S, Ratcliffe WA, Powles TJ, et al. Aminoglutethimide: metabolism and effects on steroid synthesis in vivo. Journal of Endocrinology 87: 31–32, 1980

    Google Scholar 

  • Cooper JM, Kellie AE. The metabolism of megestrol acetate (17-α-acetoxy-6-methylpregna-4,6-diene-3,20-dione) in women. Steroids 11: 133–149, 1968

    Article  PubMed  CAS  Google Scholar 

  • Cornette JC, Kirton KT, Duncan GW. Measurement of medroxyprogesterone acetate (Provera) by radioimmunoassay. Journal of Clinical Endocrinology and Metabolism 33: 459–466, 1971

    Article  PubMed  CAS  Google Scholar 

  • Crighton IL, Dowsett M, Lal A, Man A, Smith E. Use of luteinising hormone-releasing hormone agonist (leuprorelin) in advanced post-menopausal breast cancer: clinical and endocrine effects. British Journal of Cancer 60: 644–648, 1989

    Article  PubMed  CAS  Google Scholar 

  • Cunningham D, Powles TJ, Dowsett M, Hutchinson G, Brodie AMH, et al. Oral 4-hydroxyandrostenedione, a new endocrine treatment for disseminated breast cancer. Cancer Chemotherapy and Pharmacology 20: 253–255, 1987

    Article  PubMed  CAS  Google Scholar 

  • Daly MJ, Jones GW, Nicholls PJ, Smith HJ, Rowlands MG, et al. Synthesis and biochemical evaluation of analogues of aminoglutethimide based on phenylpyrrolidine-2,5-dione. Journal of Medicinal Chemistry 29: 520–523, 1986

    Article  PubMed  CAS  Google Scholar 

  • Damanhouri Z, Herbert SA, Nicholls PJ. Aminoglutethimide as an inducer of oxidative drug metabolism in the rat. Pharmacology and Therapeutics 33: 145–152, 1987a

    Article  PubMed  CAS  Google Scholar 

  • Damanhouri Z, Nicholls PJ. Acute dosing with aminoglutethimide inhibits mixed function oxidation in the mouse and rat. British Journal of Pharmacology 90: 188, 1987b

    Google Scholar 

  • Daniel CP, Gaskell SJ, Bishop H, Nicholson RI. Determination of tamoxifen and an hydroxylated metabolite in plasma from patients with advanced breast cancer using gas chromatography-mass spectrometry. Journal of Endocrinology 83: 401–408, 1979

    Article  PubMed  CAS  Google Scholar 

  • Daniel CP, Gaskell SJ, Bishop H, Campbell C, Nicholson RI. Determination of tamoxifen and biologically active metabolites in human breast tumours and plasma. European Journal of Cancer and Clinical Oncology 17: 1183–1189, 1981

    Article  CAS  Google Scholar 

  • Dechenes L. Double-blind phase II dose ranging study protocol with droloxifene. Journal of Cancer Research and Clinical Oncology 116 (Suppl.): 930, 1990

    Google Scholar 

  • Degenshein GA, Bloom N, Tobin E. The value of progesterone receptor assays in the management of advanced breast cancer. Cancer 46: 2789–2793, 1980

    Article  PubMed  CAS  Google Scholar 

  • DeGregorio MW, Wiebe VJ, Venook AP, Holleran WM. Elevated plasma tamoxifen levels in a patient with liver obstruction. Cancer Chemotherapy and Pharmacology 23: 194–195, 1989

    PubMed  CAS  Google Scholar 

  • Di Salle E, Briatico G, Giudici D, Ornati G, Zaccheo T. Aromatase inhibition and experimental antitumor activity of FCE 24304 MDL18962 and SH 489. Journal of Steroid Biochemistry 34: 431–434, 1989

    Article  PubMed  Google Scholar 

  • Donnelly RJ. Clinical uses of LHRH agonists and antagonists. In Furr & Wakeling (Eds) Pharmacology and clinical uses of inhibitors of hormone secretion and action, pp. 433–448, Baillière Tindall, London, 1987

    Google Scholar 

  • Douglas JS, Nicholls PJ. The urinary excretion of aminoglutethimide in man. Journal of Pharmacy and Pharmacology 17 (Suppl.): 115–117, 1965

    Article  Google Scholar 

  • Dowsett M, Cantwell B, Lal A, Jeffcoate SL, Harris AL. Suppression of postmenopausal ovarian steroidogenesis with the luteinizing hormone-releasing hormone agonist goserelin. Journal of Clinical Endocrinology and Metabolism 66: 672–677, 1988

    Article  PubMed  CAS  Google Scholar 

  • Dowsett M, Cunningham DC, Stein RC, Evans S, Dehennin L, et al. Dose-related endocrine effects and pharmacokinetics of oral and intramuscular 4-hydroxyandrostenedione in postmenopausal breast cancer patients. Cancer Research 49: 1306–1312, 1989

    PubMed  CAS  Google Scholar 

  • Dowsett M, Goss PE, Powles TJ, Hutchinson G, Brodie AMH, et al. Use of aromatase inhibitor 4-hydroxyandrostenedione in postmenopausal breast cancer: optimization of therapeutic dose and route. Cancer Research 47: 1957–1961, 1987

    PubMed  CAS  Google Scholar 

  • Dowsett M, Lloyd P. Comparison of the pharmacokinetics and pharmacodynamics of unformulated and formulated 4-hydroxyandrostenedione taken orally by healthy men. Cancer Chemotherapy and Pharmacology 27: 67–71, 1990

    Article  PubMed  CAS  Google Scholar 

  • Dowsett M, MacNeill F, Mehta A, Newton C, Haynes B, et al. Endocrine, pharmacokinetic and clinical studies of the aromatase inhibitor 3-ethyl-3-(4-pyridyl)piperidine-2,6-dione (‘pyridoglutethimide’) in postmenopausal breast cancer patients. British Journal of Cancer, in press, 1991

    Google Scholar 

  • Dowsett M, Mehta A, Mansi J, Smith IE. A dose-comparative endocrine-clinical study of leuprorelin in premenopausal breast cancer patients. British Journal of Cancer 62: 834–837, 1990a

    Article  PubMed  CAS  Google Scholar 

  • Dowsett M, Stein RC, Mehta A, Coombes RC. Potency and selectivity of the non-steroidal aromatase inhibitor CGS 16949A in postmenopausal breast cancer patients. Clinical Endocrinology 32: 623–634, 1990b

    Article  PubMed  CAS  Google Scholar 

  • Early Breast Cancer Trialists’ Collaborative Group. Effects of adjuvant tamoxifen and of cytotoxic therapy on mortality in early breast cancer. New England Journal of Medicine 319:1681–1692, 1988

    Article  Google Scholar 

  • Egger HP, Bartlett F, Itterly W, Rodebaugh R, Shimanskas C. Metabolism of aminoglutethimide in the rat. Drug Metabolism and Disposition 10: 405–412, 1982

    PubMed  CAS  Google Scholar 

  • Eidne KA, Flanagan CA, Millar RP. Gonadotropin-releasing hormone binding sites in human breast carcinoma. Science 229: 989–992, 1985

    Article  PubMed  CAS  Google Scholar 

  • Eweiss N, Mcholls PJ, Askam V. Absorption and elimination of aminoglutethimide in the rat and guinea pig. International Rapid Communication System Medical Science Biochemistry 11: 843–844, 1983

    CAS  Google Scholar 

  • Ewing TM, Murphy LJ, Ng ML, Pang GYN, Lee CSL, et al. Regulation of epidermal growth factor receptor by progestins and glucocorticoids in human breast cancer cell lines. International Journal of Cancer 44: 744–752, 1989

    Article  CAS  Google Scholar 

  • Fabian C, Sternson L, Barnett M. Clinical pharmacology of tamoxifen in patients with breast cancer: comparison of traditional and loading dose schedules. Cancer Treatment Reports 64: 765–773, 1980

    PubMed  CAS  Google Scholar 

  • Fabian C, Tilzer L, Sternson L. Comparative binding affinities of tamoxifen, 4-hydroxytamoxifen, and desmethyltamoxifen for estrogen receptors isolated from human breast carcinoma: correlation with blood levels in patients with metastatic breast cancer. Biopharmaceutics and Drug Disposition 2: 381–390, 1981

    Article  CAS  Google Scholar 

  • Fekete M, Wittlif JL, Schally AV. Characteristics and distribution of receptors for [D-TRP(6)]-luteinizing hormone-releasing hormone, somatostatin, epidermal growth factor, and sex steroids in 500 biopsy samples of human breast cancer. Journal of Clinical and Laboratory Analysis 3: 137–147, 1989

    Article  CAS  Google Scholar 

  • Fentiman, IS. The endocrine prevention of breast cancer. British Journal of Cancer 60: 12–14, 1989

    Article  PubMed  CAS  Google Scholar 

  • Focan C, Baudaoux A, Beauduin M, Bubescu U, Dehasque N, et al. Adjuvant treatment with high dose medroxyprogesterone acetate in node-negative early breast cancer. Acta Oncologica 28: 237–240, 1989

    Article  PubMed  CAS  Google Scholar 

  • Fornander T, Rutqvist LE. Adjuvant tamoxifen and second cancers. Lancet 1: 616, 1989

    Article  PubMed  CAS  Google Scholar 

  • Foster AB, Griggs LJ, Howe I, Jarman M, Leung C-S, et al. Metabolism of aminoglutethimide in humans: identification of four new urinary metabolites. Drug Metabolism and Disposition 12: 511–516, 1984

    PubMed  CAS  Google Scholar 

  • Foster AB, Jarman M, Leung C-S, Rowlands MG, Taylor GN, et al. Analogues of aminoglutethimide: selective inhibition of aromatase. Journal of Medical Chemistry 28: 200–204, 1985

    Article  CAS  Google Scholar 

  • Foster AB, Jarman M, Mann J, Parr IB. Metabolism of 4-hydroxyandrost-4-ene-3,17-dione by rat hepatocytes. Journal of Steroid Biochemistry 24: 607–617, 1986

    Article  PubMed  CAS  Google Scholar 

  • Fotherby K, James F. Metabolism of synthetic steroids. Advances in Steroid Biochemistry and Pharmacology 3: 67–165, 1977

    Google Scholar 

  • Fotherby K, Kamyab S, Littleton P, Klopper A. Metabolism of synthetic progestational compounds in humans. Journal of Reproduction and Fertility 5 (Suppl.): 51–61, 1968

    Google Scholar 

  • Frisch RE, Canick JA, Tulchinsky D. Human fatty marrow aromatizes androgen to estrogen. Journal of Clinical Endocrinology and Metabolism 51: 395–396, 1980

    Article  Google Scholar 

  • Fromson JM, Pearson S, Bramah S. The metabolism of tamoxifen (I.C.I. 46, 474) part II: in female patients. Xenobiotica 3: 711–714, 1973b

    Article  PubMed  CAS  Google Scholar 

  • Fromson JM, Pearson S, Bramah S. The metabolism of tamoxifen (I.C.I. 46474) part I: in laboratory animals. Xenobiotica 3: 693–709, 1973a

    Article  PubMed  CAS  Google Scholar 

  • Fromson JM, Sharp DS. The selective uptake of tamoxifen by human uterine tissue. Journal of Obstetrics and Gynecology, British Commonwealth 81: 321–323, 1974

    Article  CAS  Google Scholar 

  • Fukushima DK, Levin J, Liang JS, Smulowitz M. Isolation and partial synthesis of a new metabolite of medroxyprogesterone acetate. Steroids 34: 57–72, 1979

    Article  PubMed  CAS  Google Scholar 

  • Furr BJA, Jordan VC. The pharmacology and clinical uses of tamoxifen. Pharmacology and Therapeutics 25: 127–205, 1984

    Article  PubMed  CAS  Google Scholar 

  • Gallager CJ, Cairnduff F, Smith IE. High dose versus low dose medroxyprogesterone acetate: a randomized trial in advanced breast cancer. European Journal of Cancer and Clinical Oncology 23: 1895–1900, 1987

    Article  Google Scholar 

  • Gaskell SJ, Daniel CP, Nicholson RI. Determination of tamoxifen in rat plasma by gas chromatography-mass spectrometry. Journal of Endocrinology 78: 293–294, 1978

    Article  PubMed  CAS  Google Scholar 

  • Gaver RC, Pittman KA, Reilly CM, Smyth RD, Goodson PJ, et al. Bioequivalence evaluation of new megestrol acetate formulation in humans. Seminars in Oncology 12: 17–19, 1985

    PubMed  CAS  Google Scholar 

  • Gazet JC. Tamoxifen prophylaxis for women at high risk of breast cancer. Lancet 2: 1119, 1985

    Article  PubMed  CAS  Google Scholar 

  • Gelly C, Pasqualini JR. Effect of tamoxifen and tamoxifen derivatives on the conversion of estronesulfate to estradiol in the R-27 cells, a tamoxifen-resistant line derived from MCF-7 human breast cancer cells. Journal of Steroid Biochemistry 30: 321–324, 1988

    Article  PubMed  CAS  Google Scholar 

  • Giudici D, Ornati G, Briatico G, Buzzetti F, Lombardi P, et al. 6-Methylenandrosta 1,4-diene-3,17-dione (FCE 24304): a new irreversible aromatase inhibitor. Journal of Steroid Biochemistry 30: 391–394, 1988

    Article  PubMed  CAS  Google Scholar 

  • Golander Y, Sternson LA. Paired-ion chromatographic analysis of tamoxifen and two major metabolites in plasma. Journal of Chromatography 181: 41–49, 1989

    Google Scholar 

  • Goldenberg IS. Clinical trial of 1-testolactone (NSC 23759), medroxyprogesterone acetate (NSC 26386) and oxylone acetate (NSC 47438) in advanced female mammary cancer: a report of the Cooperative Breast Cancer Group. Cancer 23: 109–112, 1969

    Article  PubMed  CAS  Google Scholar 

  • Gorbach SL. Function of the normal human microflora. Scandinavian Journal of Infectious Diseases 49 (Suppl.): 17–30, 1986

    PubMed  CAS  Google Scholar 

  • Gordon GG, Altman K, Southren AL, Olivo J. Human hepatic testosterone A-ring reductase activity: effect of medroxyprogesterone acetate. Journal of Clinical Endocrinology and Metabolism 32: 457–461, 1971

    Article  PubMed  CAS  Google Scholar 

  • Goss PE, Jarman M, Griggs LJ. Metabolism of aminoglutethimide in humans: quantification and clinical relevance of induced metabolism. British Journal of Cancer 51: 259–262, 1985

    Article  PubMed  CAS  Google Scholar 

  • Goss PE, Jarman M, Wilkinson JR, Coombes RC. Metabolism of the aromatase inhibitor 4-hydroxyandrostenedione in vivo: identification of the glucuronide as a major urinary metabolite in patients and biliary metabolite in the rat. Journal of Steroid Biochemistry 24: 619–622, 1986a

    Article  PubMed  CAS  Google Scholar 

  • Goss PE, Powles TJ, Dowsett M, Hutchinson G, Brodie AMH, et al. Treatment of advanced postmenopausal breast cancer with an aromatase inhibitor, 4-hydroxyandrostenedione: phase II report. Cancer Research 46: 4823–4826, 1986b

    PubMed  CAS  Google Scholar 

  • Gottardis MM, Robinson SP, Satyaswaroop PG, Jordan VC. Contrasting actions of tamoxifen on endometrial and breast tumor growth in the athymic mouse. Cancer Research 48: 812–815, 1988

    PubMed  CAS  Google Scholar 

  • Graves PE, Salhanick HA. Stereoselective inhibition of aromatase by enantiomers of aminoglutethimide. Endocrinology 105: 52–57, 1979

    Article  PubMed  CAS  Google Scholar 

  • Grill HJ, Pollow K. Pharmacokinetics of droloxifene and its metabolites in breast cancer patients. American Journal of Clinical Oncology 14 (Suppl.): 21–29, 1991

    Article  Google Scholar 

  • Guarna A, Moneti G, Prucher D, Salerno R, Serio M. Quantitative determination of 4 hydroxy-4-androstene-3,17-dione (4-OHA), a potent aromatase inhibitor, in human plasma, using isotope dilution mass spectrometry. Journal of Steroid Biochemistry 32: 699–702, 1989

    Article  PubMed  CAS  Google Scholar 

  • Gundersen S. Toremifene, a new antiestrogenic compound in the treatment of metastatic mammary cancer: a phase II study. Journal of Steroid Biochemistry 36: 233–234, 1990

    Article  PubMed  CAS  Google Scholar 

  • Gundersen S, Kvinnsland S. Chemotherapy in advanced breast cancer. Acta Radiologica (Oncology) 25: 1–7, 1986

    Article  Google Scholar 

  • Gupta C, Musto NA, Bullock LP, Nahrwold D, Osterman J, et al. In vivo metabolism of progestins II: metabolic clearance rate of medroxyprogesterone acetate in four species. In Garattini & Berendes (Eds) Pharmacology of steroid contraceptive drugs, pp. 131–136, Raven Press, New York, 1977

    Google Scholar 

  • Gupta C, Osterman J, Santen R, Wayne Bardin C. In vivo metabolism of progestins vs the effect of protocol design on the estimated metabolic clearance rate and volume of distribution of medroxyprogesterone acetate in women. Journal of Clinical Endocrinology and Metabolism 48: 816–820, 1979

    Article  PubMed  CAS  Google Scholar 

  • Gurpide E, Tseng L, Gusberg SB. Estrogen metabolism in normal and neoplastic endometrium. American Journal of Obstetrics and Gynecology 129: 809–816, 1977

    PubMed  CAS  Google Scholar 

  • Haarstad H, Gundersen S, Lønning PE, Raabe N, Wist E, Kvinnsland S. Influence of droloxifene on metastatic breast cancer as first line therapy. European Journal of Cancer 27 (Suppl. 2): 68, 1991

    Google Scholar 

  • Hamm JT, Tormey DC, Kohler PC, Haller C, Green M, et al. Phase I study of toremifene in patients with advanced breast cancer. Journal of Clinical Oncology 9: 2036–2041, 1991

    PubMed  CAS  Google Scholar 

  • Harris AL, Carmichael J, Cantwell BMJ, Dowsett M. Zoladex: endocrine and therapeutic effects in post-menopausal breast cancer. British Journal of Cancer 59: 97–99, 1989

    Article  PubMed  CAS  Google Scholar 

  • Harris AL, Dowsett M, Jeffcoate SL, McKinna A, Morgan M, Smith IE, et al. Endocrine and therapeutic effects of aminoglutethimide in premenopausal patients with breast cancer. Journal of Clinical Endocrinology and Metabolism 55: 713–722, 1982

    Google Scholar 

  • Hartmann RW, Batzl C, Mannschreck A, Pongratz T. Stereoselective aromatase inhibition by the enantiomers of 3-cyclohexyl-3-(4-aminophenyl)-2,6-piperidinedione. In Hulmstedt et al. (Eds) Chirality and biological activity, pp. 185–190, Alan R. Liss, Inc., New York, 1990

    Google Scholar 

  • Harvey HA, Lipton A, Max DT. LH-RH agonist treatment of breast cancer: a phase II study in the USA. In Klijn et al. (Eds) Hormonal manipulation of cancer, pp. 321–330, Raven Press, New York, 1987

    Google Scholar 

  • Harvey HA, Lipton A, White DS, Santen RJ, Boucher AE, et al. Cross-over comparison of tamoxifen and aminoglutethimide in advanced breast cancer. Cancer Research 42 (Suppl.): 3451–3453, 1982

    Google Scholar 

  • Harvey H. Clinical experience with the third generation aromatase inhibitors. 15th International Cancer Congress, Hamburg, August 16–22, 1990

  • Haynes BP, Jarman M, Dowsett M, Mehta A, Lønning PE, et al. Pharmacokinetics and pharmacodynamics of the aromatase inhibitor 3-ethyl-3(4-pyridyl)piperidine-2,6-dione in patients with postmenopausal breast cancer. Cancer Chemotherapy and Pharmacology 27: 367–372, 1991

    Article  PubMed  CAS  Google Scholar 

  • Hayward JL, Rubens RD, Carbone PP, Heuson JC, Kumaoka S, et al. Assessment of response to therapy in advanced breast cancer. British Journal of Cancer 35: 292, 1977

    Article  PubMed  CAS  Google Scholar 

  • Hedley DW, Christie M, Weatherby RP, Caterson ID. Lack of correlations between plasma concentration of medroxyprogesterone acetate, hypothalamic-pituitary function and tumor response in patients with advanced breast cancer. Cancer Chemotherapy and Pharmacology 14: 112–115, 1985

    Article  PubMed  CAS  Google Scholar 

  • Henderson IC. Chemotherapy of breast cancer: a general overview. Cancer 51: 2553–2559, 1983

    Article  PubMed  CAS  Google Scholar 

  • Henderson IC. Endocrine therapy in metastatic breast cancer. In Harris et al. (Eds) Breast diseases, pp. 398–428, Lippincott, Philadelphia, 1987

    Google Scholar 

  • Hietanen T, Baltina D, Johansson R, Numminen S, Hakala T, et al. High dose toremifene (240 mg daily) is effective as first line hormonal treatment in advanced breast cancer: an ongoing phase II multicenter Finnish-Latvian cooperative study. BreastyCancer Research and Treatment 16 (Suppl.): 37–40, 1990

    Google Scholar 

  • Hindy I, Juhos E, Szanto J, Szamel I. Effect of toremifene in breast cancer, patients: preliminary communication. Journal of Steroid Biochemistry 36: 225–226, 1990

    Article  PubMed  CAS  Google Scholar 

  • Hiroi M, Stanczyk FZ, Goebelsmann U, Brenner PF, Lumkin ME, et al. Radioimmunoassay of serum medroxyprogesterone acetate in women following oral and intravaginal administration. Steroids 26: 373–386, 1975

    Article  PubMed  CAS  Google Scholar 

  • Høffken K, Becher R, Kurschel E, Doberauer C, Anders CU, et al. Buserelin in the treatment of premenopausal patients with advanced breast cancer. In Høffken (Ed.) LHRH agonists in oncology, pp. 149–162, Springer, Berlin, 1988

    Chapter  Google Scholar 

  • Høffken K, Jonat W, Possinger K, Kolbel M, Kunz T, et al. Aromatase inhibition with 4-hydroxyandrostenedione in the treatment of postmenopausal patients with advanced breast cancer: a phase II study. Journal of Clinical Oncology 8: 875–880, 1990

    PubMed  Google Scholar 

  • Holland FJ, Fishman L, Costigan DC, Luna L, Leeder S. Pharmacokinetic characteristics of the gonadotropin-releasing hormone analog D-Ser(TBU)-6EA-10 luteinizing hormone-releasing hormone (buserelin) after subcutaneous and intranasal administration in children with central precocious puberty. Journal of Clinical Endocrinology and Metabolism 63: 1065–1070, 1986

    Article  PubMed  CAS  Google Scholar 

  • Holleran WM, Gharbo SA, DeGregorio MW. Quantitation of toremifene and its major metabolites in human plasma by high-performance liquid chromatography following fluorescent activation. Analytical Letters 20: 871–879, 1987

    Article  CAS  Google Scholar 

  • Holtkamp DE, Greslin JG, Root, CA, Lerner LJ. Gonadotrophin inhibiting and antifecundity effects of chloramiphene. Proceedings of the Society for Experimental Biology and Medicine 105: 197–201, 1960

    PubMed  CAS  Google Scholar 

  • Horgan K, Cooke E, Hallett MB, Mansel RE. Inhibition of protein kinase C mediated signal transduction by tamoxifen. Biochemical Pharmacology 35: 4463–4465, 1986

    Article  PubMed  CAS  Google Scholar 

  • Horwitz KB, Wei LL, Sedlacek SM, D’Arville CN. Progestin action and progesterone receptor structure in human breast cancer: a review. Recent Progress in Hormone Research 41: 249–316, 1985

    PubMed  CAS  Google Scholar 

  • Hsueh AJW, Jones PBC. Extrapituitary actions of gonadotropin releasing hormone. Endocrine Review 1: 437–461, 1981

    Article  Google Scholar 

  • Huber HJ, Stanislaus F. Pharmacokinetics and metabolism of 3-hydroxy-tamoxifen citrate in laboratory animals. Poster demonstration, Deutschen Pharmazeutischen Gesellschrift, Düsseldorf, Sept. 1984

    Google Scholar 

  • Hutchinson FG, Furr BJA. Sustained-release formulations of LHRH analogues. In Furr & Wakeling (Eds) Pharmacology and clinical uses of inhibitors of hormone secretion and action, pp. 409–431, Baillière Tindal, 1987

    Google Scholar 

  • Hutchinson FG, Furr BJA. Biodegradable polymer systems for the sustained release of polypeptides. Journal of Controlled Release 13: 279–294, 1990

    Article  CAS  Google Scholar 

  • Iacobelli S, Sica G, Natoli C, Gatti D. Inhibitory effect of medroxyprogesterone acetate on the proliferation of human breast cancer cells. In Campio et al. (Eds) Role of medroxyprogesterone in endocrine-related tumors, pp. 1–6, Raven Press, New York, 1983

    Google Scholar 

  • Ingle JN, Ahmann DL, Green SJ, Edmonson JH, Creagan ET, et al. Randomized clinical trial of megestrol acetate versus tamoxifen in paramenopausal or castrated women with advanced breast cancer. American Journal of Clinical Oncology 5: 155–160, 1982

    Article  PubMed  CAS  Google Scholar 

  • Jakobsen A, Frederiiksen PL, Møller KA, Andersen AP, Brincker H, et al. Medroxyprogesterone acetate and prednisone in advanced breast cancer: a randomized trial. European Journal of Cancer and Clinical Oncology 22: 1067–1072, 1986

    Article  CAS  Google Scholar 

  • Jarman M, Foster AB, Goss PE, Griggs LJ, Howhe I, et al. Metabolism of aminoglutethimide in humans: identification of hydroxylaminoglutethimide as an induced metabolite. Biomedical Mass Spectrometry 10: 620–625, 1983

    Article  PubMed  CAS  Google Scholar 

  • Johannessen DC, Lønning PE. Aromatase inhibitors in malignant diseases of aging. Drugs and Aging, in press, 1991

    Google Scholar 

  • Johnson PA, Bonomi PD, Anderson KM, Wolter JM, Economou SG. Megestrol acetate: first-line therapy for advanced breast cancer. Seminars in Oncology 13: 15–19, 1986

    PubMed  CAS  Google Scholar 

  • Jordan VC. Biochemical pharmacology of antiestrogen action. Pharmacological Reviews 36: 245–276, 1984

    PubMed  CAS  Google Scholar 

  • Jordan VC, Bain RR, Brown RR, Gosden B, Santos MA. Determination and pharmacology of a new hydroxylated metabolite of tamoxifen observed in patient sera during therapy for advanced breast cancer. Cancer Research 43: 1446–1450, 1983

    PubMed  CAS  Google Scholar 

  • Jordan VC, Collins MM, Rowsby L, Prestwich G. A monohydroxylated metabolite of tamoxifen with potent antiestrogenic activity. Journal of Endocrinology 75: 305–316, 1977a

    Article  PubMed  CAS  Google Scholar 

  • Jordan VC, Dix CJ, Rowsby L, Prestwich G, Studies on the mechanism of action of the non-steroidal antiestrogen tamoxifen (I.C.I. 46,474) in the rat. Molecular and Cellular Endocrinology 7: 177–192, 1977b

    Article  PubMed  CAS  Google Scholar 

  • Jordan VC, Lababidi MK, Mirecki DM. Anti-oestrogenic and antitumor properties of prolonged tamoxifen therapy in CH3/OUJ mice. European Journal of Cancer 26: 718–721, 1990

    Article  PubMed  CAS  Google Scholar 

  • Kaiser DG, Carlson RG, Kirton KT. GLC detemination of medroxyprogesterone acetate in plasma. Journal of Pharmaceutical Sciences 63: 420–424, 1974

    Article  PubMed  CAS  Google Scholar 

  • Kangas L. Biochemical and pharmacological effects of toremifene metabolites. Cancer Chemotherapy and Pharmacology 27: 8–12, 1990c

    Article  PubMed  CAS  Google Scholar 

  • Kangas L. Introduction to toremifene. Breast Cancer Research and Treatment 16 (Suppl.): 3–7, 1990a

    Article  Google Scholar 

  • Kangas L. Review of the pharmacological properties of toremifene. Journal of Steroid Biochemistry 36: 191–195, 1990b

    Article  PubMed  CAS  Google Scholar 

  • Kangas L, Haaparanta M, Paul R, Roeda D, Sipila H. Biodistribution and scintigraphy of 11C-toremifene in rats bearing DMBA-induced mammary carcinoma. Pharmacology and Toxicology 64: 373–377, 1989

    Article  PubMed  CAS  Google Scholar 

  • Kemp JV, Adam HK, Wakeling AE, Slater R. Identification and biological activity of tamoxifen metabolites in human serum. Biochemical Pharmacology 32: 2045–2052, 1983

    Article  PubMed  CAS  Google Scholar 

  • Khubieh J, Aherne GW, Chakraborty J. Radioimmunoassay of the anticancer agent 4-hydroxy-androstenedione in body fluids. Journal of Steroid Biochemistry 35: 377–382, 1990b

    Article  PubMed  CAS  Google Scholar 

  • Khubieh J, Aherne GW, Chakraborty J. Serum kinetics of the anti-cancer agent 4-hydroxyandrostenedione in the rat. Cancer Chemotherapy and Pharmacology 26: 330–332, 1990a

    Article  PubMed  CAS  Google Scholar 

  • Kiesel L, Sandow J, Bertges K, Jerabek-Sandow G, Trabant H, Runnebaum B. Serum concentration and urinary excretion of the luteinizing hormone-releasing hormone agonist buserelin in patients with endometriosis. Journal of Clinical Endocrinology and Metabolism 68: 1167–1173, 1989

    Article  PubMed  CAS  Google Scholar 

  • Kincl FA, Angee I, Chang CL, Rudel HW. Plasma levels and accumulation into various tissues of 6-methyl-17a-acetoxy-4,6-pregnandiene-3,20-dione after oral administration or absorption from polydimethyl-siloxane implants. Acta Endocrinologica 64: 508–518, 1970

    PubMed  CAS  Google Scholar 

  • Kistner RW, Smith OW. Observations on the use of a non-steroidal estrogen antagonist: MER-25. Surgical Forum 10: 725–729, 1960

    PubMed  CAS  Google Scholar 

  • Klijn JGM, de Jong FH. Treatment with luteinizing-hormone releasing hormone analogue (buserelin) in premenopausal patients with metastatic breast cancer. Lancet 1: 1213–1216, 1982

    Article  PubMed  CAS  Google Scholar 

  • Klijn JGM, de Jong FH, Blankenstein MA, et al. Anti-tumor and endocrine effects of chronic LHRH agonist treatment (buserelin) with or without tamoxifen in premenopausal metastatic breast cancer. Breast Cancer Research and Treatment 4: 209–220, 1984

    Article  PubMed  CAS  Google Scholar 

  • Klijn JGM, de Jong FH, Lamberts SWJ, Blankenstein MA. LHRH-agonist treatment in clinical and experimental human breast cancer. Journal of Steroid Biochemistry 23: 867–873, 1985

    Article  PubMed  CAS  Google Scholar 

  • Knobil E. The neuroendocrine control of the menstrual cycle. Recent Progress in Hormone Research 36: 53–88, 1980

    PubMed  CAS  Google Scholar 

  • Kochak GM, Mangat S, Mulagha MT, Entwistle EA, Santen RJ, et al. The pharmacodynamic inhibition of estrogen synthesis by fadrozole, an aromatase inhibitor, and its pharmacokinetic disposition. Journal of Clinical Endocrinology and Metabolism 71: 1349–1355, 1990

    Article  PubMed  CAS  Google Scholar 

  • Kohler PC, Hamm JT, Wiebe VJ, DeGregorio MV, Shemano I, et al. Phase I study of the tolerance and pharmacokinetics of toremifene in patients with cancer. Breast Cancer Research and Treatment 16 (Suppl.): 19–26, 1990

    Article  Google Scholar 

  • Langan-Fahey SM, Douglass C, Tormey DC, Jordan VC. Tamoxifen metabolites in patients on long-term adjuvant therapy for breast cancer. European Journal of Cancer 26: 883–888, 1990

    Article  PubMed  CAS  Google Scholar 

  • Lau CK, Subramaniam M, Rasmussen K, Speisberg TC. Rapid induction of the c-protooncogene in the avian oviduct by the antiestrogen tamoxifen. Proceedings of the National Academy of Science of the United States 88: 829–833, 1991

    Article  CAS  Google Scholar 

  • Lefevre F-A, Reeves JJ, Sequin C, Massicotte J, Labrie F. Specific binding of a potent LHRH agonist in rat testis. Molecular and Cellular Endocrinology 20: 127–135, 1980

    Article  Google Scholar 

  • Legha SS, Carter SK. Antiestrogens in the treatment of breast cancer. Cancer Treatment Reviews 3: 205–216, 1976

    Article  PubMed  CAS  Google Scholar 

  • Lerner LJ, Holthaus FJJ, Thompson CR. A non-steroidal estrogen antagonist (1-(p-2-diethylaminoethoxyphenyl)-1-phenyl-2-p-methoxyphenyl-ethanol. Endocrinology 63: 295–318, 1958

    Article  PubMed  CAS  Google Scholar 

  • Lerner LJ, Jordan VC. Development of antiestrogens and their use in breast cancer: eighth Cain memorial award lecture. Cancer Research 50: 4177–4189, 1990

    PubMed  CAS  Google Scholar 

  • Lien EA, Anker G, Lønning PE, Solheim E, Ueland PM. Decreased serum concentrations of tamoxifen and its metabolites induced by aminoglutethimide. Cancer Research 50: 5851–5857, 1990

    PubMed  CAS  Google Scholar 

  • Lien EA, Solheim E, Kvinnsland S, Ueland PM. Identification of 4-hydroxy-N-desmethyl-tamoxifen as a metabolite of tamoxifen in human bile. Cancer Research 48: 2304–2308, 1988

    PubMed  CAS  Google Scholar 

  • Lien EA, Solheim E, Lea OA, Lundgren S, Kvinnsland S, et al. Distribution of 4-hydroxy-N-desmethyltamoxifen and other tamoxifen metabolites in human biological fluids during tamoxifen treatment. Cancer Research 49: 2175–2183, 1989

    PubMed  CAS  Google Scholar 

  • Lien EA, Solheim E, Ueland PM. Distribution of tamoxifen and its metabolites in rat and human tissues during steady state treatment. Cancer Research 51: 4837–4844, 1991a

    PubMed  CAS  Google Scholar 

  • Lien EA, Ueland PM, Solheim E, Kvinnsland S. Determination of tamoxifen and four metabolites in serum by low-dispersion liquid chromatography. Clinical Chemistry 33: 1608–1614, 1987

    PubMed  CAS  Google Scholar 

  • Lien EA, Wester K, Lønning PE, Solheim E, Ueland PM. Distribution of tamoxifen and metabolites into brain tissue and brain metastases in breast cancer patients. British Journal of Cancer 63: 641–645, 1991b

    Article  PubMed  CAS  Google Scholar 

  • Lipton A, Harvey HA, Demers LM, Hanagan JR, Mulagha MT, et al. A phase I trial of CGS 16949A: a new aromatase inhibitor. Cancer 65: 1279–1285, 1990

    Article  PubMed  CAS  Google Scholar 

  • Lipton A, Harvey HA, Santen RJ, Boucher A, White D, et al. Randomized trial of aminoglutethimide versus tamoxifen in metastatic breast cancer. Cancer Research 42 (Suppl.): 3434–3436, 1982

    Google Scholar 

  • Liscowitch M, Koch Y. Characterization and subcellular localization of GnRH analog binding in rat brain. Peptides 3: 55–61, 1982

    Article  Google Scholar 

  • Lodwick R, McConkey B, Brown AM, Beeley L. Life threatening interactions between tamoxifen and warfarin. British Medical Journal 295: 1141, 1987

    Article  PubMed  CAS  Google Scholar 

  • Lopes MCF, Vale MGP, Carvalho AP. Ca2+-dependent binding of tamoxifen to calmodulin isolated from bovine brain. Cancer Research 50: 2753–2758, 1990

    PubMed  CAS  Google Scholar 

  • Love RR, Newcomb PA, Wiebe DA, Surawicz TS, Jordan VC, et al. Effects of tamoxifen therapy on lipid and lipoprotein levels in postmenopausal patients with node-negative breast cancer. Journal of the National Cancer Institute 82: 1327–1332, 1990

    Article  PubMed  CAS  Google Scholar 

  • Lundgren S, Gundersen S, Klepp R, Lønning PE, Lund E, et al. Megestrol acetate versus aminoglutethimide for metastatic breast cancer. Breast Cancer Research and Treatment 14: 201–206, 1989a

    Article  PubMed  CAS  Google Scholar 

  • Lundgren S, Kvinnsland S, Utaaker E. Oral high-dose progestins as treatment for advanced breast cancer. Acta Oncologica 28: 811–816, 1989b

    Article  PubMed  CAS  Google Scholar 

  • Lundgren S, Kvinnsland S, Utaaker E, Bakke O, Ueland PM. Effect of oral high dose progestins on the disposition of antipyrine, digitoxin and warfarin in patients with advanced breast cancer. Cancer Chemotherapy and Pharmacology 18: 270–275, 1986

    Article  PubMed  CAS  Google Scholar 

  • Lundgren S, Lønning PE. Influence of progestins on serum hormone levels in postmenopausal women with advanced breast cancer II: a differential effect of megestrol acetate and medroxyprogesterone acetate on serum estrone sulfate and sex hormone binding globuline. Journal of Steroid Biochemistry 36: 105–109, 1990

    Article  PubMed  CAS  Google Scholar 

  • Lundgren S, Lønning PE, Aakvaag A, Kvinnsland S. Influence of aminoglutethimide on the metabolism of medroxyprogesterone acetate and megestrol acetate in postmenopausal patients with advanced breast cancer. Cancer Chemotherapy and Pharmacology 27: 101–105, 1990a

    Article  PubMed  CAS  Google Scholar 

  • Lundgren S, Lønning PE, Utaaker E, Aakvaag A, Kvinnsland S. Influence of progestins on serum hormone levels in postmenopausal women with advanced breast cancer I: general findings. Journal of Steroid Biochemistry 36: 99–104, 1990b

    Article  PubMed  CAS  Google Scholar 

  • Lyman SD, Jordan VC. Metabolism of nonsteroidal antiestrogens. In Jordan (Ed.) Estrogen/antiestrogen action and breast cancer therapy, pp. 191–219, University of Wisconsin Press, Madison, 1986

    Google Scholar 

  • Löser R, Seibel K, Ross W, Eppenberger U. In vivo and in vitro antiestrogenic action of 3-hydroxytamoxifen, tamoxifen and 4-hydroxytamoxifen. European Journal of Cancer and Clinical Oncology 21: 985–990, 1985

    Article  Google Scholar 

  • Løber J, Mouridsen HT, Salimtschik M, Johansson E. Pharmacokinetics of medroxyprogesterone acetate administered by oral and intramuscular route. Acta Obstetrica et Gynecologica Scandinavica 101 (Suppl.): 71–74, 1981

    Article  Google Scholar 

  • Lønning PE, Dowsett M, Powles TJ. Postmenopausal estrogen synthesis and metabolism: alterations caused by aromatase inhibitors used for the treatment of breast cancer. Journal of Steroid Biochemistry 35: 355–366, 1990

    Article  PubMed  Google Scholar 

  • Lønning PE, Jacobs S, Jones A, Haynes B, Powles T, et al. The influence of CGS 16949A on peripheral aromatisation in breast cancer patients. British Journal of Cancer 63: 789–793, 1991

    Article  PubMed  Google Scholar 

  • Lønning PE, Kvinnsland S. Mechanisms of action of aminoglutethimide as endocrine therapy of breast cancer. Drugs 35: 685–710, 1988

    Article  PubMed  Google Scholar 

  • Lønning PE, Kvinnsland S, Bakke OM. Effect of aminoglutethimide on antipyrine, theophylline, and digitoxin disposition in breast cancer. Clinical Pharmacology and Therapeutics 36: 796–802, 1984

    Article  PubMed  Google Scholar 

  • Lønning PE, Kvinnsland S, Thorsen T, Ueland PI. Alterations in the metabolism of oestrogens during treatment with aminoglutethimide in breast cancer patients preliminary findings. Clinical Pharmacokinetics 13: 393–406, 1987

    Article  PubMed  Google Scholar 

  • Lønning PE, Schanche JS, Kvinnsland S, Ueland PM. Single-dose and steady-state pharmacokinetics of aminoglutethimide. Clinical Pharmacokinetics 10: 353–364, 1985

    Article  PubMed  Google Scholar 

  • Lønning PE, Ueland PM, Kvinnsland S. The influence of a graded dose schedule of aminoglutethimide on the disposition of the optical enantiomers of warfarin in patients with breast cancer. Cancer Chemotherapy and Pharmacology 17: 177–181, 1986

    Article  PubMed  Google Scholar 

  • Major JS, Green B, Heald PJ. Interactions of oestradiol-17β and tamoxifen in the uterus of the pregnant rat. Journal of Endocrinology 71: 315–324, 1976

    Article  PubMed  CAS  Google Scholar 

  • Manni A, Arafah BM. Tamoxifen-induced remission in breast cancer by escalating the dose to 40 mg daily after progression on 20 mg daily: a case report and review of the literature. Cancer 48: 873–875, 1981

    Article  PubMed  CAS  Google Scholar 

  • Marsh DA, Romanoff L, Williams KIH, Brodie HJ, Brodie AMH. Synthesis of deuterium- and tritium-labeled 4-hydroxyandros-tene-3,17-dione, an aromatase inhibitor, and its metabolism in vitro and in vivo in the rat. Biochemical Pharmacology 31: 701–705, 1982

    Article  PubMed  CAS  Google Scholar 

  • Martin F, Adlercreutz H. Aspects of megestrol acetate and medroxyprogesterone acetate metabolism. In Garattini & Berendes (Eds) Pharmacology of steroid contraceptive drugs, pp. 99–115, Raven Press, New York, 1977

    Google Scholar 

  • Mathrubutham M, Fotherby K. Medroxyprogesterone acetate in human serum. Journal of Steroid Biochemistry 114: 783–786, 1981

    Article  Google Scholar 

  • Matlin SA, Thomas C, Vince PM. Anti-hormonal agents VI: direct plasma analyses of tamoxifen by HPLC using an on-line ISRP extraction cartridge. Journal of Liquid Chromatography 13: 2253–2260, 1990

    Article  CAS  Google Scholar 

  • Matsumine H, Hirato K, Yanaihara T, Tamada T, Yoshida M. Aromatization by skeletal muscle. Journal of Clinical Endocrinology and Metabolism 63: 717–720, 1986

    Article  PubMed  CAS  Google Scholar 

  • Mauvais-Jarvis P, Baudot N, Castaigne D, Banzet P, Kuttenn F. Trans-4-hydroxytamoxifen concentration and metabolism after local percutaneous administration to human breast. Cancer Research 46: 1521–1525, 1986

    Google Scholar 

  • McDonald CC, Stewart HJ. Fatal myocardial infarction in the Scottish adjuvant tamoxifen trial. British Medical Journal 303: 435–437, 1991

    Article  PubMed  CAS  Google Scholar 

  • McGuire WL. Steroid receptors in human breast cancer. Cancer Research 38: 4289–4291, 1978

    PubMed  CAS  Google Scholar 

  • Meitzer NM, Stang P, Sternson LA. Influence of tamoxifen and its N-desmethyl and 4-hydroxy metabolites on rat liver microsomal enzymes. Biochemical Pharmacology 33: 115–123, 1984

    Article  Google Scholar 

  • Mendenhall DW, Kobayashi H, Shih FML, Sternson LA, Higuchi T, et al. Clinical analysis of tamoxifen, an anti-neoplastic agent, in plasma. Clinical Chemistry 24: 1518–1524, 1978

    PubMed  CAS  Google Scholar 

  • Menge G, Dubois JP. Determination of aminoglutethimide and N-acetylaminoglutethimide in human plasma by high-performance liquid chromatography. Journal of Chromatography 310: 431–437, 1984

    Article  PubMed  CAS  Google Scholar 

  • Middeke M, Remien C, Lohmøller G, Holzgreve H, Zollner N. Interaction between tamoxifen and digitoxin? Klinische Wochenschrift 64: 1211, 1986

    Article  Google Scholar 

  • Milano G, Carle G, Renee N, Boublil JL, Namer M. Determination of medroxyprogesterone acetate in plasma by high-performance liquid chromatography. Journal of Chromatography 232: 413–417, 1982

    Article  PubMed  CAS  Google Scholar 

  • Milano G, Etienne MC, Frenay M, Khater R, Formento JL, et al. Optimised analysis of tamoxifen and its main metabolites in the plasma and cytosol of mammary tumours. British Journal of Cancer 55: 509–512, 1987

    Article  PubMed  CAS  Google Scholar 

  • Miller AA, Miller BE, Hoffken K, Schmidt CG. Clinical pharmacology of aminoglutethimide in patients with metastatic breast cancer. Cancer Chemotherapy and Pharmacology 20: 337–341, 1987

    Article  PubMed  CAS  Google Scholar 

  • Miller WR, Anderson TJ, Jack WJL. Relationship between tumour aromatase activity, tumour characteristics and response to therapy. Journal of Steroid Biochemistry 37: 1055–1059, 1990

    Article  CAS  Google Scholar 

  • Modig H, Borgstrom S, Nilsson I, Westman G. Phase II clinical study of high-dose toremifene in patients with advanced breast cancer. Journal of Steroid Biochemistry 36: 237–238, 1990

    Article  PubMed  CAS  Google Scholar 

  • Morgan LR. Megestrol acetate v tamoxifen in advanced breast cancer in postmenopausal patients. Seminars in Oncology 12: 43, 1985

    PubMed  CAS  Google Scholar 

  • Murphy C, Fotsis T, Pantzar P, Adlercreutz H, Martin F. Analysis of tamoxifen and its metabolites in human plasma by gas chromatography-mass spectrometry (GCMS) using selected ion monitoring (SIM). Journal of Steroid Biochemistry 26: 547–555, 1987

    Article  PubMed  CAS  Google Scholar 

  • Murray FT, Santner S, Samojlik E, Santen RJ. Serum aminoglutethimide levels: studies of serum half-life, clearance, and patient compliance. Journal of Clinical Pharmacology 19: 704–711, 1979

    PubMed  CAS  Google Scholar 

  • Muss HB, Paschold EH, Black WR, Cooper MR, Capizzi RL, et al. Megestrol acetate v. tamoxifen in advanced breast cancer: a phase III trial of the Piedmont Oncology Association (POA). Seminars in Oncology 12: 55–61, 1985

    PubMed  CAS  Google Scholar 

  • Nestor Jr JJ. Development of agonistic LHRH analogs. In Vickery et al. (Eds) LHRH and its analogs: a new class of contraceptive and therapeutic agents, pp. 3–10, MTP Press, Lancaster, 1984

    Google Scholar 

  • Nicholls PJ. Pharmacokinetic and balance studies of aminoglutethimide in animals and man. Royal Society of Medicine, International Congress and Symposium Series 53: 23–24, 1982

    Google Scholar 

  • Nicholson RI, Maynard. Antitumour activity of ICI 118630, a new potent luteinizing hormone releasing hormone agonist. British Journal of Cancer 39: 268–273, 1979

    Article  PubMed  CAS  Google Scholar 

  • Nicholson RI, Walker KJ. Use of LH-RH agonists in the treatment of breast cancer. Proceedings of the Royal Society of Edinburgh 95B: 271–281, 1989

    Google Scholar 

  • Nieder M, Jaeger H. Quantification of tamoxifen and N-desme-thyltamoxifen in human plasma by high-performance liquid chromatography, photochemical reaction and fluorescence detection, and its application to biopharmaceutical investigations. Journal of Chromatography 413: 207–217, 1987

    Article  PubMed  CAS  Google Scholar 

  • Nillius SJ. The therapeutic uses of gonadotrophin-releasing hormone and its analogues. In Beardwell & Robertson (Eds) Clinical endocrinology 1: the pituitary, pp. 211–237, Butterworths, London, 1981

    Google Scholar 

  • Nishino Y, Schneider MR, Michna H, El Etreby MF. Antitumor effect of a specific aromatase inhibitor, 1-methyl-androsta-1,4-diene-3,17-dione (atamestane), in female rats bearing DMBA-induced mammary tumors. Journal of Steroid Biochemistry 34: 435–437, 1989

    Article  PubMed  CAS  Google Scholar 

  • Noguchi S, Miyauchi K, Imaoka S, Koyama H. Inability of tamoxifen to penetrate into cerebrospinal fluid. Breast Cancer Research and Treatment 12: 317–318, 1988

    Article  PubMed  CAS  Google Scholar 

  • Ogilvie ML, Casida LE, First NL, Hoekstra WG. Tissue incorporation and excretion of tritium labelled progestins in rabbits, sheep and swine. Journal of Animal Science 24: 1051–1060, 1965

    CAS  Google Scholar 

  • O’Brian CA, Liskamp RM, Solomon DH, Weinstein IB. Inhibition of protein kinase C by tamoxifen. Cancer Research 45: 2462–2465, 1985

    PubMed  Google Scholar 

  • Pagani C. 6-Methyl-6-dehydro-17, a-hydroxyprogesterone acetate and uterine dynamic (experimental study). Annals of Obstetrics 83: 387–392, 1961

    CAS  Google Scholar 

  • Pannuti F, Camaggi CM, Strocchi E, Giovannini M, Di Marco AR, et al. Medroxyprogesterone acetate (MPA) relative bioavailability after single high-dose administration in cancer patients. Cancer Treatment Reports 66: 2043–2049, 1982

    PubMed  CAS  Google Scholar 

  • Pannuti F, Camaggi CM, Strocchi E, Martoni A, Beghelli P, et al. Medroxyprogesterone acetate pharmacokinetics. In Pelligrini et al. (Eds) Role of medroxyprogesterone in endocrine-related tumors, pp. 43–77, Raven Press, New York, 1984

    Google Scholar 

  • Pannuti F, Martoni A, Cilenti G, Camaggi CM, Fruet P. Adjuvant therapy for operable breast cancer with medroxyprogesterone alone in postmenopausal patients or in combination with CMF in premenopausal patients. European Journal of Cancer and Clinical Oncology 24: 423–429, 1988

    Article  CAS  Google Scholar 

  • Pannuti F, Martoni A, Di Marco AR, Piana E, Saccani F, et al. Prospective, randomized clinical trial of two different high dosages of medroxyprogesterone acetate (MAP) in the treatment of metastatic breast cancer. European Journal of Cancer 15: 593–601, 1979

    Article  PubMed  CAS  Google Scholar 

  • Pannuti F, Martoni A, Lenaz GR, Piana E, Nanni P. A possible new approach to the treatment of metastatic breast cancer: massive doses of medroxyprogesterone acetate. Cancer Treatment Reports 62: 499–504, 1978

    PubMed  CAS  Google Scholar 

  • Paridaens R, Becquart D, Michel J, Vanderlinden B, Longueville J, et al. Oral vesus intramuscular high-dose medroxyprogesterone acetate (HD-MPA) in advanced breast cancer. Anticancer Research 6: 1089–1094, 1986

    PubMed  CAS  Google Scholar 

  • Parker Jr CR, Foreman MM, Porter JC. Subcellular localization of luteinizing hormone-releasing hormone degrading activity in the hypothalamus. Brain research 174: 221–228, 1979

    Article  PubMed  CAS  Google Scholar 

  • Pasqualini JR, Gelly C. Effect of tamoxifen and tamoxifen derivatives on the conversion of estrone sulfate to estradiol in the MCF-7 mammary cancer cell line. Cancer Letters 40: 115–121, 1988

    Article  PubMed  CAS  Google Scholar 

  • Patterson J, Furr B, Wakeling A, Battersby L. The biology and physiology of ‘Nolvadex’ (tamoxifen) in the treatment of breast cancer. Breast Cancer Research and Treatment 2: 363–374, 1982

    Article  Google Scholar 

  • Patterson JS, Settatree RS, Adam HK, Kemp JV. Serum concentrations of tamoxifen and major metabolite during long term nolvadex therapy, correlated with clinical response In Mouridsen & Palshof (Eds), Breast cancer: experimental and clinical aspects, pp. 89–92, Pergamon Press, Oxford, 1980

    Google Scholar 

  • Perel E, Killinger DW. The interconversion and aromatization of androgens by human adipose tissue. Journal of Steroid Biochemistry 10: 623–627, 1979

    Article  PubMed  CAS  Google Scholar 

  • Perren TJ, Clayton RN, Blackledge G, Bailey LC, Holder G, et al. Pharmacokinetic and endocrinological parameters of a slow-release depot preparation of the GnRH analogue ICI 118630 (Zoladex) compared with a subcutaneous bolus and continuous subcutaneous infusion of the same drug in patients with prostatic cancer. Cancer Chemotherapy and Pharmacology 18: 39–43, 1986

    Article  PubMed  CAS  Google Scholar 

  • Phillippou G, Frith RG. Specific quantitation of plasma medroxyprogesterone acetate by gas chromatography/mass spectrometry. Clinica Chimica Acta 103: 129–133, 1980

    Article  Google Scholar 

  • Pickles T, Perry L, Murraay, Plowman P. 4-Hydroxyandrostenedione — further clinical and extended endocrine observations. British Journal of Cancer 62: 309–313, 1990

    Article  PubMed  CAS  Google Scholar 

  • Plowman PN, Nicholson RI, Walker KJ. Remission of postmenopausal breast cancer during treatment with the luteinising hormone releasing hormone agonist ICI 118630. British Journal of Cancer 54: 903–909, 1986

    Article  PubMed  CAS  Google Scholar 

  • Poon GK, Jarman M, Rowlands MG, Dowsett M, Firth J. Determination of 4-hydroxyandrost-4-ene-3, 17-dione metabolism in breast cancer patients using high-performance liquid chromatography-mass spectrometry. Journal of Chromatography 565: 75–88, 1991

    Article  PubMed  CAS  Google Scholar 

  • Pyrhonen SO. Phase III studies of toremifene in metastatic breast cancer. Breast Cancer Research and Treatment 16 (Suppl.): 41–46, 1990

    Article  Google Scholar 

  • Reed MJ, Lai LC, Owen AM, Singh A, Coldham NG, et al. Effect of treatment with 4-hydroxyandrostenedione on the peripheral conversion of androstenedione to estrone and in vitro tumor aromatase activity in postmenopausal women with breast cancer. Cancer Research 50: 193–196, 1990

    PubMed  CAS  Google Scholar 

  • Ritchie LD, Grant SMT. Tamoxifen-warfarin interaction: the Aberdeen hospitals drug file. British Medical Journal 298: 1253, 1989

    Article  PubMed  CAS  Google Scholar 

  • Robertson DW, Katzenellenbogen JA, Long DJ, Rorke EA, Katzenellenbogen BS. Tamoxifen antiestrogens: a comparison of the activity, pharmacokinetics, and metabolic activation of the cis and trans isomers of tamoxifen. Journal of Steroid Biochemistry 16: 1–13, 1982

    Article  PubMed  CAS  Google Scholar 

  • Robertson JFR, Nicholson RJ, Walker KJ, Blamey RW. Zoladex in advanced breast cancer. Hormone Research 32 (Suppl. 1): 206–208, 1989

    Article  PubMed  Google Scholar 

  • Robinson BA, Cornell FN. Liquid-chromatographic determination of aminoglutethimide in plasma. Clinical Chemistry 29: 1104–1105, 1983

    PubMed  CAS  Google Scholar 

  • Robinson SP, Jordan VC. Anti-steroidal agents. In Powis & Prough (Eds) Metabolism and action of anti-cancer drugs, pp. 261–295, Taylor & Francis, London, 1987

    Google Scholar 

  • Robinson SP, Jordan VC. Metabolism of steroid-modifying anticancer agents. Pharmacological Therapeutics 36: 41–103, 1988

    Article  CAS  Google Scholar 

  • Robinson SP, Langan-Fahey SM, Johnson DA, Jordan VC. Metabolites, pharmacodynamics, and pharmacokinetics of tamoxifen in rats and mice compared to the breast cancer patient. Drug Metabolism and Disposition 19: 36–43, 1991

    PubMed  CAS  Google Scholar 

  • Rossi E, De Pascale A, Negrini P, Frigerio A. Quantitative gas-liquid chromatographic determination of medroxyprogesterone acetate in human plasma. Journal of Chromatography 169: 416–421, 1979

    Article  PubMed  CAS  Google Scholar 

  • Rossner S, Wallgren A. Serum lipoproteins and proteins after breast cancer surgery and effects of tamoxifen. Atherosclerosis 52: 339–346, 1984

    Article  PubMed  CAS  Google Scholar 

  • Rowland M, Tozer TN. Clinical pharmacokinetics: concepts and applications, Lea & Febiger, Philadelphia, 1980

    Google Scholar 

  • Rowlands MG, Bunnett MA, Foster AB, Jarman M, Stanek J, et al. Analogues of aminoglutethimide based on 1-phenyl-3-aza-bicyclo [3-1.0]hexane-2,4-dione: selective inhibition of aromatase activity. Journal of Medicinal Chemistry 31: 971–976, 1988

    Article  PubMed  CAS  Google Scholar 

  • Rowlands MG, Parr IB, McCague R, Jarman M, Goddard PM. Variation in the inhibition of calmodulin dependent cyclic AMP phosphodiesterase amongst analogues of tamoxifen: correlations with cytotoxicity. Biochemical Pharmacology 40: 283–289, 1990

    Article  PubMed  CAS  Google Scholar 

  • Royer ME, Ko H, Campbell JA, Murray HC, Evans JS, et al. Radioimmunoassay for medroxyprogesterone acetate (Provera®) using the 11α-hydroxysuccinyl conjugate. Steroids 23: 713–730, 1974

    Article  PubMed  CAS  Google Scholar 

  • Ruenitz PC, Bagley JR. Comparative fates of clomiphene and tamoxifen in the immature female rat. Drug Metabolism and Disposition 13: 582–586, 1985

    PubMed  CAS  Google Scholar 

  • Ruenitz PC, Bagley JR, Pape CW. Some chemical and biochemical aspects of liver microsomal metabolism of tamoxifen. Drug Metabolism and Disposition 12: 478–483, 1984

    PubMed  CAS  Google Scholar 

  • Rutqvist LE. Increasing incidence and constant mortality rates of breast cancer: item trends in Stockholm County 1961–1973. Breast Cancer Research and Treatment 4: 233–243, 1984

    Article  PubMed  CAS  Google Scholar 

  • Sala G, Camerino B, Calvallero C. Progestational activity of 6α-methyl-17α-hydroxyprogesterone acetate. Acta Endocrinologica 29: 508–512, 1958

    PubMed  CAS  Google Scholar 

  • Sandow J. Pharmacology of LHRH agonists. In Furr & Wakeling (Eds) Pharmacology and clinical uses of inhibitors of hormone secretion and action, pp. 365–384, Baillière Tindall, London, 1987

    Google Scholar 

  • Sandow J, Jerzabek G, Stoll W, Kuhl H. Metabolism of 125Iluteinizing hormone releasing hormone analogue (buserelin) in rats in vivo and in vitro. Journal of Endocrinology 85: 11, 1980

    Google Scholar 

  • Sandow J, Konig W. Studies with fragments of a highly active analogue of luteinising hormone releasing hormone. Journal of Endocrinology 81: 175–182, 1979

    Article  PubMed  CAS  Google Scholar 

  • Sandow J, Seidel B, Krauss B, Jerabek-Sandow G. Pharmacokinetics of LHRH agonists in different delivery systems and the relation to endocrine function. In Keyn et al. (Eds) Hormonal manipulation of cancer: peptides, growth factors and new (anti) steroidal agents, pp. 203–211, Raven Press, New York, 1987

    Google Scholar 

  • Santen RJ, Demers LM, Adlercreutz H, Harvey H, Santner S, et al. Inhibition of aromatase with CGS 16949 in postmenopausal women. Journal of Clinical Endocrinology and Metabolism 68: 99–106, 1989

    Article  PubMed  CAS  Google Scholar 

  • Santen RJ, Lipton A, Kendall J. Successful medical adrenalectomy with aminoglutethimide. Journal of the American Medical Association 230: 1661–1665, 1974

    Article  PubMed  CAS  Google Scholar 

  • Santen RJ, Manni A, Harvey H, Redmond C. Endocrine treatment of breast cancer in women. Endocrine Reviews 11: 221–265, 990

  • Santen RJ, Samojlik E, Wells SA. Resistance of the ovary to blockade of aromatization with aminoglutethimide. Journal of Clinical Endocrinology and Metabolism 51: 473–477, 1980

    Article  PubMed  CAS  Google Scholar 

  • Santen RJ, Santner S, Davis B, Veldhuis J, Samojlik E, et al. Aminoglute-thimide inhibits extraglandular estrogen production in postmenopausal women with breast carcinoma. Journal of Clinical Endocrinology and Metabolism 47: 1257–1265, 1978

    Article  PubMed  CAS  Google Scholar 

  • Santen RJ, Worgul TJ, Lipton A, Harvey H, Boucher A, et al. Aminoglutethimide as treatment of postmenopausal women with advanced breast carcinoma. Annals of Internal Medicine 96: 94–101, 1982

    PubMed  CAS  Google Scholar 

  • Schally AV, Arimura A, Kastin AJ, Matsuo H, Baba Y, et al. Gonadotrophin-releasing hormone: one polypeptide regulates secretion of lutenizing and follicle-stimulating hormone. Science 173: 1036–1037, 1971

    Article  PubMed  CAS  Google Scholar 

  • Schanche J-S, LØnning PE, Ueland PM, Kvinnsland S. Determination of aminoglutethimide and n-acetylaminoglutethimide in human plasma by reversed phase liquid chromatography. Therapeutic Drug Monitoring 6: 221–226, 1984

    Article  PubMed  CAS  Google Scholar 

  • Schieweck K, Bhatnagar AS, Matter A. CGS 16949A, a new non-steriodal aromatase inhibitor: effects on hormone-dependent and -independent tumors in vivo. Cancer Research 48: 834–838, 1988

    PubMed  CAS  Google Scholar 

  • Schweikert HU, Milewich L, Wilson JD. Aromatization of androstenedione by cultured human fibroblasts. Journal of Clinical Endocrinology and Metabolism 40: 413–417, 1975

    Article  PubMed  CAS  Google Scholar 

  • Schweikert HU, Milewich L, Wilson JD. Aromatization of androstenedione by isolated human hairs. Journal of Clinical Endocrinology and Metabolism 43: 785–795, 1976

    Article  PubMed  CAS  Google Scholar 

  • Seago A, Goss PE, Griggs LJ, Jarman M. Pyridoglutethimide [3-ethyl-3-(4-pyridyl)-piperidine-2,6-dione], an analogue of aminoglutethimide. Biochemical Pharmacology 35: 2911–2916, 1986

    Article  PubMed  CAS  Google Scholar 

  • Sedlacek SM, Horwitz KB. The role of progestins and progesterone receptors in the treatment of breast cancer. Steroids 44: 467–484, 1984

    Article  PubMed  CAS  Google Scholar 

  • Segalof A, Cuningham M, Rice BF, Weeth JB. Hormonal therapy in cancer of the breast XIV: effect of corticosterone of medroxyprogesterone acetate on clinical course and hormonal excretion. Cancer 20: 1673–1678, 1957

    Article  Google Scholar 

  • Sheth SP, Allegra JC. Endocrine therapy of breast cancer. In Bland & Copeland (Eds) The breast: comprehensive management of benign and malignant diseases, Saunders, Philadelphia, 1991

    Google Scholar 

  • Simberg NH, Murai JT, Siiteri PK. In vitro and in vivo binding of toremifene and its metabolites in rat uterus. Journal of Steroid Biochemistry 36: 197–202, 1990

    Article  PubMed  CAS  Google Scholar 

  • Sipilä H, Kangas L, Vuorilehto L, Kalapudas A, Eloranta M, et al. Metabolism of toremifene in the rat. Journal of Steroid Biochemistry 36: 211–215, 1990

    Article  PubMed  Google Scholar 

  • Sipilä H, Nanto V, Kangas L, Anttila M, Halme T. Binding of toremifene to human serum proteins. Pharmacology and Toxicology 63: 62–64, 1988

    Article  PubMed  Google Scholar 

  • Sirtori CR, De Fabiani E, Caruso D, Malavasi B, Galli G, et al. Single dose pharmacokinetics of aminoglutethimide by a rapid SIM methodology. International Journal of Clinical Pharmacology, Therapy and Toxicology 26: 380–384, 1988

    CAS  Google Scholar 

  • Sjøholm I, Ekman B, Kober A, Ljungstedt-Pahlmam I, Seiving B, et al. Binding of drugs to human serum albumin XI. Molecular Pharmacology 16: 767–777, 1979

    PubMed  Google Scholar 

  • Slaunwhite WR, Sandberg AA. Disposition of radioactive 17a-hydroxyprogesterone, 6a-methyl-prednisolone in human subjects. Journal of Clinical Endocrinology and Metabolism 21: 753–764, 1961

    Article  CAS  Google Scholar 

  • Sletholt K. Radioimmunoassay of 6a-acetoxyprogesterone (MPA) in plasma of sheep during and after oral administration. Acta Endocrinologica 96: 141–144, 1981

    PubMed  CAS  Google Scholar 

  • Smith IE, Harris AL, Morgan M, Ford HT, Gazet J-C, et al. Tamoxifen versus aminoglutethimide in advanced breast carcinoma: a randomized cross-over trial. British Medical Journal 283: 1432–1434, 1981

    Article  PubMed  CAS  Google Scholar 

  • Smith JF, Fairclough RJ, Peterson AJ. Plasma levels of progesterone, Provera, oestradiol-17β, and 13,14-dihydro-15-keto-prostaglandin F in cow treated with Provera-impregnated intravaginal sponges. Journal of Reproduction and Fertility 55: 359–364, 1979

    Article  PubMed  CAS  Google Scholar 

  • Smuk M, Schwers J. Aromatization of androstenedione by human adult liver in vitro. Journal of Clinical Endocrinology and Metabolism 45: 1001–1012, 1977

    Article  Google Scholar 

  • Spicer DV, Pike MC, Henderson BE, Groshen S. Tamoxifen and estrogen replacement therapy as agents of disease prevention. Journal of the National Cancer Institute 83: 63–64, 1991

    Article  PubMed  CAS  Google Scholar 

  • Stamm H, Roth R, Huber H-J, Jank P, Loser R, et al. Preliminary data on a phase-I trial of the new antiestrogen droloxifene: tolerance, pharmacokinetics and metabolism. Contributions to Oncology 23: 73–78, 1986

    Google Scholar 

  • Steele RE, Mellor LB, Sawyer WK, Wasvary JM, Browne LJ. In vitro and in vivo studies demonstrating potent and selective estrogen inhibition with the nonsteroidal aromatase inhibitor CGS 16949A. Steroids 50: 147–161, 1987

    Article  PubMed  CAS  Google Scholar 

  • Stein RC, Dowsett M, Davenport J, Hedley A, Ford HT, et al. Preliminary study of the treatment of advanced breast cancer in postmenopausal women with the aromatase inhibitor CGS 16949A. Cancer Research 50: 1381–1384, 1990

    PubMed  CAS  Google Scholar 

  • Stevenson D, Briggs RJ, Chapman DJ, de Vos D. Determination of tamoxifen and five metabolites in plasma. Journal of Pharmaceutical and Biomedical Analysis 6: 1065–1068, 1988

    Article  PubMed  CAS  Google Scholar 

  • Stockdale AD, Chapman D, Mould GP, Rostom AY. Medroxyprogesterone acetate: variation in serum concentration achieved with three commercially available preparations. Cancer Treatment Reports 71: 813–815, 1987

    PubMed  CAS  Google Scholar 

  • Stoll BA. Progestin therapy of breast cancer: comparison of agents. British Medical Journal 3: 338–341, 1967

    Article  PubMed  CAS  Google Scholar 

  • Stuart-Harris R, Bradbrook I, Morrison P, Smith E, Rogers HJ. Observations on the pharmacokinetics of low dose aminoglutethimide in patients with advanced breast cancer. British Journal of Cancer 51: 485–492, 1985

    Article  PubMed  CAS  Google Scholar 

  • Sturm G, Haberlein H, Bauer T, Plaum T, Stalker DJ. Mass spectrometric and high-performance liquid chromatographic studies of medroxyprogesterone acetate metabolites in human plasma. Journal of Chromatography 562: 351–362, 1991

    Article  PubMed  CAS  Google Scholar 

  • Sutherland CM, Sternson LA, Muchmore JH, Ball JE, Cerise EJ. Effect of impaired renal function on tamoxifen. Journal of Surgical Oncology 27: 222–223, 1984

    Article  PubMed  CAS  Google Scholar 

  • Sutherland RL, Murphy LC, Foo MS, Green MD, Whybourne AM. High-affinity antioestrogen binding site distinct from the oestrogen receptor. Nature 288: 273–275, 1980

    Article  PubMed  CAS  Google Scholar 

  • Swain SM, Lippman ME. Endocrine therapies of cancer. In Chabner & Collins (Eds) Cancer chemotherapy: principles and practice, pp. 59–109, JB Lippincott Company, Philadelphia, 1990

    Google Scholar 

  • Tenni P, Laiich DL, Byrne MJ. Life threatening interaction between tamoxifen and warfarin. British Journal of Medicine 298: 93, 1989

    Article  CAS  Google Scholar 

  • Thompson TA, Vermeulen JD, Wagner Jr WE, LeSher AR. Aminoglutethimide bioavailability, pharmacokinetics, and binding to blood constituents. Journal of Pharmaceutical Sciences 70: 1040–1043, 1981

    Article  PubMed  CAS  Google Scholar 

  • Tilson-Mallett N, Santner SJ, Feil PD, Santen RJ. Biological significance of aromatase activity in human breast tumors. Journal of Clinical Endocrinology and Metabolism 57: 1125–1128, 1983

    Article  PubMed  CAS  Google Scholar 

  • Tominaga T, Abe O, Izuo M, Nomura Y. A phase I study of toremifene. Breast Cancer Research and Treatment 16 (Suppl.): 27–29, 1990

    Article  Google Scholar 

  • Tseng L, Gurpide E. Effect of progestins on estradiol receptor levels in human endometrium. Journal of Clinical Endocrinology and Metabolism 41: 402–404, 1975a

    Article  PubMed  CAS  Google Scholar 

  • Tseng L, Gurpide E. Induction of human endometrial estradiol dehydrogenase by progestins. Endocrinology 97: 825–833, 1975b

    Article  PubMed  CAS  Google Scholar 

  • Tukker JJ, Blankenstein MA, Nortier JWR. Decreased bioavailability of tamoxifen after rectal administration. European Journal of Cancer and Clinical Oncology 22: 1083–1084, 1986

    Article  CAS  Google Scholar 

  • Utaaker E, Lundgren S, Kvinnsland S, Aakvaag A. Pharmacokinetics and metabolism of medroxyprogesterone acetate in patients with advanced breast cancer. Journal of Steroid Biochemistry 31: 437–441, 1988

    Article  PubMed  CAS  Google Scholar 

  • Valavaara R, Pyrhonen S, Heikkinen M, Rissanen P, Blanco G. Toremifene, a new antiestrogenic compound, for treatment of advanced breast cancer: phase II study. European Journal of Cancer and Clinical Oncology 24: 785–790, 1988

    Article  CAS  Google Scholar 

  • Van Deijk WA, Blijham GH, Mellink WAM, Meulenberg PMM. Influence of aminoglutethimide on plasma levels of medroxyprogesterone acetate: its correlation with serum Cortisol. Cancer Treatment Reports 69: 85–90, 1985

    PubMed  Google Scholar 

  • Van Veelen H, Willemse PHB, Sleijfer DT, van der Ploeg E, Sluiter WJ, et al. Mechanism of adrenal suppression by high-dose medroxyprogesterone acetate in breast cancer patients. Cancer Chemotherapy and Pharmacology 15: 167–170, 1985

    Article  PubMed  Google Scholar 

  • Van Veelen H, Willemse PH, Tjabbes T, Schweitzer MJ, Sleijfer DT. Oral high-dose medroxyprogesterone acetate versus tamoxifen: a randomised crossover trial in postmenopausal patients with advanced breast cancer. Cancer 58: 7–19, 1986

    Article  PubMed  Google Scholar 

  • Vermeulen A. The hormonal activity of the postmenopausal ovary. Journal of Clinical Endocrinology and Metabolism 42: 247–253, 1976

    Article  PubMed  CAS  Google Scholar 

  • Vermeulen A, Paridaens R, Heuson JC. Effects of aminoglutethimide on adrenal steroid secretion. Clinical Endocrinology 19: 673–682, 1983

    Article  PubMed  CAS  Google Scholar 

  • Victor A, Johansson EDB. Pharmacokinetic observations on medroxyprogesterone acetate administered orally and intravaginally. Contraception 14: 319–329, 1976

    Article  PubMed  CAS  Google Scholar 

  • Vollenweider-Zerargui L, Barrelet L, Wong Y, Lemarchand-Béraud T, Gomez F. The predictive value of estrogen and progesterone receptors’ concentrations on the clinical behaviour of breast cancer in women. Cancer 7: 1171–1180, 1986

    Article  Google Scholar 

  • Wander HE, Kleeberg UR, Gartner E, Gartner E, Hartlapp J, et al. Megestrol acetate versus medroxyprogesterone acetate in the treatment of metastasizing carcinoma of the breast. Onkologie 10: 104–106, 1987

    Article  PubMed  CAS  Google Scholar 

  • Watanabe N, Irie T, Koyama M. Liquid chromatographic atmospheric pressure ionization mass spectrometric analysis of toremifene metabolites in human urine. Journal of Chromatography 497: 169, 180, 1989

    Article  PubMed  CAS  Google Scholar 

  • Watkins SM. The value of high dose tamoxifen in postmenopausal breast cancer patients progressing on standard dose: a pilot study. British Journal of Cancer 57: 320–321, 1988

    Article  PubMed  CAS  Google Scholar 

  • Webster LK, Crinis NA, Stokes KH, Bishop JF. High-performance liquid chromatographic method for the determination of toremifene and its major human metabolites. Journal of Chromatography 565: 482–487, 1991

    Article  PubMed  CAS  Google Scholar 

  • Webster NJG, Green S, Jin JR, Chambon P. The hormone-binding domains of the estrogen and glucocorticoid receptors contain an inducible transcription activation function. Cell 54: 199–207, 1988

    Article  PubMed  CAS  Google Scholar 

  • Wiebe VJ, Benz CC, Shemano I, Cadman TB, DeGregorio MW. Pharmacokinetics of toremifene and its metabolites in patients with advanced breast cancer. Cancer Chemotherapy and Pharmacology 25: 257–251, 1990

    Article  Google Scholar 

  • Wilbur BJ, Benz CC, DeGregorio MW. Quantitation of tamoxifen, 4-hydroxytamoxifen, and N-desmethyltamoxifen in human plasma by high performance liquid chromotography. Analytical Letters 18: 1915–1924, 1985

    Article  CAS  Google Scholar 

  • Wilking N, Appelgren E, Carlstrøm K, Nordgren T, Theve T. The distribution and metabolism of 14C-labelled tamoxifen in spayed female mice. Reviews on Endocrinological Related Cancer 9: 233–239, 1981

    Google Scholar 

  • Willemse PHB, van der Ploeg E, Sleijfer DT, Tjabbes T, van Veelen H. A randomised comparison of megestrol acetate (MA) and medroxyprogesterone acetate (MPA) in patients with advanced breast cancer. European Journal of Cancer 26: 337–343, 1990

    Article  PubMed  CAS  Google Scholar 

  • Wing L-Y, Garrett WM, Brodie AMH. Effects of aromatase inhibitors, aminoglutethimide, and 4-hydroxyandrostenedione on cyclic rats and rats with 7,12-dimethylbenz(a)anthracene-induced mammary tumors. Cancer Research 45: 2425–2428, 1985

    PubMed  CAS  Google Scholar 

  • Wolter J, Ryan WG, Subbaiah PV, Bagdade JD. Apparent beneficial effects of tamoxifen on serum lipoprotein subfractions and bone mineral content in patients with breast cancer. Proceedings of the Society for Clinical Oncology 7: 10, 1988

    Google Scholar 

  • Wouters W, De Coster R, Tuman RW, Bowden CR, Bruynseels J, et al. Aromatase inhibition by R 767113: experimental and clinical pharmacology. Journal of Steroid Biochemistry 34: 427–430, 1989

    Article  PubMed  CAS  Google Scholar 

  • Zbuzkova V, Kincl FA. Substained release hormonal preparations. Plasma levels of 6-methyl-17a-acetoxy-4,6-pregnadiene-3,20-dione in hamsters. Steroids 16: 447–450, 1970

    Article  Google Scholar 

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Lønning, P.E., Lien, E.A., Lundgren, S. et al. Clinical Pharmacokinetics of Endocrine Agents Used in Advanced Breast Cancer. Clin. Pharmacokinet. 22, 327–358 (1992). https://doi.org/10.2165/00003088-199222050-00002

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