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Aromatase Inhibitors in Malignant Diseases of Aging

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  • Clinical Pharmacology
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Summary

Aromatase inhibition is an established endocrine treatment modality in postmenopausal breast cancer and is currently considered as an interesting experimental treatment approach in other malignant conditions such as endometrial carcinomas and prostatic cancer. While the ‘classic’ aromatase inhibitor aminoglutethimide causes many adverse effects that makes it unfit for use in elderly patients, several novel aromatase inhibitors with minimal adverse effects are currently being investigated. These drugs may provide important new tools in the endocrine treatment of malignant diseases in aging patients.

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References

  • Abul-Hajj YJ. The effect of the aromatase inhibitor, 4-(phenylthiol)-4androstene-3, 17-dione, on dimethylbenz(A)anthraceneinduced rat mammary tumours. Journal of Steroid Biochemistry and Molecular Biology 34: 439–442, 1989

    CAS  Google Scholar 

  • Ahmann FR, Crawford ED, Kreis W, Levasseur Y, The Aminoglutethimide Study Group. Adrenal steroid levels in castrated men with prostatic carcinoma treated with aminoglutethimide plus hydrocortisone. Cancer Research 47: 4736–4739, 1987

    PubMed  CAS  Google Scholar 

  • Alberto P, Mermillod B, Kaplan E, Goldhirsh A, Obrecht JP, et al. A clinical trial of aminoglutethimide in advanced postmenopausal breast carcinoma: low response in patients previously treated with medroxyprogesterone. European Journal of Cancer and Clinical Oncology 21: 423–428, 1985

    Article  CAS  Google Scholar 

  • Asbury RF, Bakemeier RF, Folsch E, McCune CS, Savlov E, et al. Treatment of metastatic breast cancer with aminoglutethimide. Cancer 47: 1954–1958, 1981

    Article  PubMed  CAS  Google Scholar 

  • Baker HW, Burger HG, de Kretser DM, Hudson B, O’Connor S, et al. Changes in the pituitary-testicular system with age. Clinical Endocrinology 5: 349–372, 1976

    Article  PubMed  CAS  Google Scholar 

  • Barone RM, Shamoniki IM, Siiteri PK, Judd HL. Inhibition of peripheral aromatization of androstenedione to estrone in postmenopausal women with breast cancer using deltab1-testolactone. Journal of Clinical Endocrinology and Metabolism 49: 672–676, 1979

    Article  PubMed  CAS  Google Scholar 

  • Bashirelahi N, Young JD, Sidh SM, Sanefuji H. Androgen, estrogen and their distribution in epithelial and stromal cells of human prostate. In Schroeder & deVoogt (Eds) Steroid receptors, metabolism and prostatic cancer, pp. 240–255, Excerpta Medica, Amsterdam, 1980

    Google Scholar 

  • Beretta KR, Höffken K, Kvinnsland S, Trunet P, Bhatnagar AS, 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 

  • Blackard CE, Byer DF, Jordan WP. Orchiectomy for advanced prostatic carcinoma. Urology 1: 553–562, 1973

    Article  PubMed  CAS  Google Scholar 

  • Block M, Trumph D, Ropse P, Cummings KB, Hogan TF. Evaluation of aminoglutethimide in stage prostate cancer: an assessment of efficacy and toxicity in patients with tumours refractory to hormonal treatment. Cancer Treatment Reports 68: 719–722, 1984

    PubMed  CAS  Google Scholar 

  • Bolt HM. Metabolism of estrogens — natural and synthetic. Pharmacology and Therapeutics 4: 155–181, 1979

    Article  PubMed  CAS  Google Scholar 

  • Bonneterre J, Coppens H, Mauriac L, Metz M, Rouesse J, et al. Aminoglutethimide in advanced breast cancer: clinical results of a French multicenter randomized trial comparing 500mg and 1 g/day. European Journal of Cancer and Clinical Oncology 21: 1155–1158, 1985

    Article  Google Scholar 

  • Brodie AMH, Schwarzel WC, Saikh AA, Brodie H. The effect of an aromatase inhibitor, 4-hydroxy-4-androstene-3, l7-dione, on estrogen dependent processes in reproduction and breast cancer. Endocrinology 100: 1684–1695, 1977

    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 

  • Brufman G, Brian S. Aminoglutethimide as second line endocrine treatment in metastatic breast cancer. Tumori 71: 297–300, 1986

    Google Scholar 

  • Bruning PF, Bonfer JMG, Engelsman E, Hamersmavd Linden E, De Jong-Bakker M, et al. Pros and cons of aminoglutethimide for advanced postmenopausal breast cancer. Breast Cancer Research Treatment 4: 289–295, 1984

    Article  CAS  Google Scholar 

  • Bruning PF, Bonfer JMG, Hart AAM, van der Linden E, de Jong-Bakker M, et al. Low dose aminoglutethimide without hydrocortisone for the treatment of advanced postmenopausal breast cancer. European Journal of Cancer and Clinical Oncology 25: 369–376, 1989

    Article  CAS  Google Scholar 

  • Buzdar AU, Powell KC, Blumenschein GR. Aminoglutethimide after tamoxifen therapy in advanced breast cancer. M.D. Anderson Hospital experience. Cancer Research 42 (Suppl.): 3448–3450, 1982

    Google Scholar 

  • Cagle PT, Mody R, Schwartz MR. Estrogen and progesterone receptors in bronchogenic carcinoma. Cancer Research 50: 6632–6635, 1990

    PubMed  CAS  Google Scholar 

  • Camacho AM, Cash R, Brough AJ, Wilroy RS. Inhibition of adrenal steroidgenesis by aminoglutethimide and the mechanism of action. Journal of the American Medical Association 202: 114–120, 1967

    Article  CAS  Google Scholar 

  • Canney PA, Priestman TJ, Griffits 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) as an inhibitor of adrenal steroidgenesis: mechanism of action and therapeutic trial. Journal of Clinical Endocrinology 27: 1239–1248, 1967

    Article  CAS  Google Scholar 

  • Clark JH, Paszko Z, Peck EJ. Nuclear binding and retention of the receptor estrogen complex: relation to the agonistic and antagonistic properties of estriol. Endocrinology 100: 91–96, 1977

    Article  PubMed  CAS  Google Scholar 

  • Coombes RC. 4-hydroxyandrostenedione treatment for advanced breast cancer. 15th International Cancer Congress, August 16–22, Hamburg, 1990

    Google Scholar 

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

    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 

  • Dao TL-Y, Huggins CB. Bilateral adrenalectomy in the treatment of cancer of the breast. Archives of Surgery 71: 645–657, 1955

    Article  PubMed  Google Scholar 

  • Demers LM, Boucher AE, Santen RJ. Aminoglutethimide therapy in breast cancer: relationship of blood levels to drug-related side effects. Clinical Physiology and Biochemistry 5: 287–291, 1987

    PubMed  CAS  Google Scholar 

  • Di Salle E, Briatico G, Guidici D. Aromatase inhibition and experimental antitumor activity of FCE 24304, MDL 18962 and SH 489. Journal of Steroid Biochemistry 34: 431–434, 1989

    Article  PubMed  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-hydroxy androstenedione in postmenopausal breast cancer patients. Cancer Research 49: 1306–1312, 1989

    PubMed  CAS  Google Scholar 

  • Dowsett M, Harris AL, Stuart-Harris R. A comparison of the endocrine effects of low dose aminoglutethimide with and without hydrocortisone in postmenopausal breast cancer patients. British Journal of Cancer 52: 525–529, 1985

    Article  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, Shearer RJ, Ponder BAJ, Malone P, Jeffcoate SL. The effects of aminoglutethimide and hydrocortisone, alone and combined, on androgen levels in post-orchidectomy prostatic cancer patients. British Journal of Cancer 57: 190–192, 1988

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Drago JR, Santen R, Lipton A, Worgul TJ, Harvey HA, et al. Clinical effect of aminoglutethimide, medical adrenalectomy, in treatment of 43 patients with advanced prostatic carcinoma. Cancer 53: 1447–1450, 1984

    Article  PubMed  CAS  Google Scholar 

  • Elomaa I, Blomquist C, Rissanen P. Aminoglutethimide as second-line therapy in advanced breast cancer. Breast Cancer Research Treatment 7 (Suppl.): 51–54, 1986

    Article  Google Scholar 

  • Fishman J, Schneider J, Hershcopf RJ, Bradlow HL. Increased estrogen-16-alfahydroxylase activity in women with breast and endometrial cancer. Journal of Steroid Biochemistry 20: 1077–1081, 1984

    Article  PubMed  CAS  Google Scholar 

  • Fishman J, Nisselbaum JS, Menenez-Botet CJ, Schwartz MK. Estrone and estradiol content in human breast tumours: relationship to estradiol receptor. Journal of Steroid Biochemistry 8: 893–896, 1977

    Article  PubMed  CAS  Google Scholar 

  • Franz C, Watson D, Longcope C. Estrone sulfate and dehydroepiandrosterone sulfate concentrations in normal subjects and men with cirrhosis. Steroids 34: 563–574, 1979

    Article  PubMed  CAS  Google Scholar 

  • Gale KE. Treatment of advanced breast cancer with aminoglutethimide: a 14-year experience. Cancer Research 42 (Suppl.): 3389–3396, 1982

    Google Scholar 

  • Geller J, Albert JD. Adrenal androgen blockade in relapsed prostatic cancer. European Journal of Cancer and Clinical Oncology 21: 1127–1131, 1985

    Article  CAS  Google Scholar 

  • Geller J, Albert JD, Loza D, Geller S, Stoeltzing W, et al. DHT concentrations in human prostate cancer tissue. Journal of Clinical Endocrinology and Metabolism 46: 440–444, 1978

    Article  PubMed  CAS  Google Scholar 

  • Gennatas CS, Kalovidorius A, Paraskevas GA, Kouvaris J, Trichopoulus D, et al. A randomised phase II trial of aminoglutethimide and hydrocortisone versus combined aminoglutethimide, hydrocortisone and fluoxymesterone in advanced breast cancer. Radiotherapy and Oncology 9: 217–220, 1987

    Article  PubMed  CAS  Google Scholar 

  • Gerber SB, Miller KB. Cholestatic jaundice and aminoglutethimide. Annals of Internal Medicine 97: 138, 1982

    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 the rat. Journal of Steroid Biochemistry 24: 619–622, 1985

    Article  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-hydroxyandrostendione: phase II report. Cancer Research 46: 4823–4826, 1986

    PubMed  CAS  Google Scholar 

  • Greenway B, Igball MJ, Johnson PJ, Williams R. Oestrogen receptor proteins in malignant and foetal pancreas. British Medical Journal 283: 751–753, 1981

    Article  PubMed  CAS  Google Scholar 

  • Griffits CT, Hall TC, Saba Z, Barlow JJ, Nevhinny HB, et al. Preliminary trial of aminoglutethimide in breast cancer. Cancer 32: 31–37, 1973

    Article  Google Scholar 

  • Grodin JM, Siiteri PK, MacDonald PC. Source of estrogen production in postmenopausal women. Journal of Clinical Endocrinology and Metabolism 36: 207–214, 1973

    Article  PubMed  CAS  Google Scholar 

  • Halper J, Colvard DS, Scheithauer BW, Jiang NS, Press MF, et al. Estrogen and progesterone receptors in meningiomas: comparison of nuclear binding, dextran-coated charcoal, and immunoperoxidase staining assays. Neurosurgery 25: 546–553, 1989

    Article  PubMed  CAS  Google Scholar 

  • Harris A, Cantwell BM, Carmichael J, Dawes P, Robinson A, et al. Phase II study of low dose aminoglutethimide 250 mg/day plus hydrocortisone in advanced postmenopausal breast cancer. European Journal of Cancer and Clinical Oncology 25: 1105–1111, 1989

    Article  CAS  Google Scholar 

  • Harris A, Dowsett M, Jeffcoate SL, McKinna JA, Morgan M, et al. Endocrine and therapeutic effects of aminoglutethimide in premenopausal patients with breast cancer. Journal of Clinical Endocrinology and Metabolism 55: 718–722, 1982b

    Article  PubMed  CAS  Google Scholar 

  • Harris AL, Mitchell MD, Smith IE, Powles TJ. Suppression of plasma 6-keto-prostaglandin F1-alfa and 13, 14-dihydro-15-keto-prostaglandin F2-alfa by aminoglutethimide in advanced breast cancer. British Journal of Cancer 48: 595–598, 1983

    Article  PubMed  CAS  Google Scholar 

  • Harris AL, Powles TJ, Smith IE. Aminoglutethimide in the treatment of advanced postmenopausal breast cancer. Cancer Research 42 (Suppl.): 3405S–3408S, 1982a

    PubMed  CAS  Google Scholar 

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

    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

    Google Scholar 

  • Harvey H, Lipton A, Simmons M, Santen R, Bartholomew M. Chemotherapy and aromatase inhibition in metastatic melanoma. Process Annual Meeting American Society of Clinical Oncology 7: A978, 1988

    Google Scholar 

  • Harvey H, Santen R, Osterman J, Samojlik E, White DS, et al. A comparative trial of transsphenoidal hypophysectomy and estrogen suppression with aminoglutethimide in advanced breast cancer. Cancer 43: 2207–2214, 1979

    Article  PubMed  CAS  Google Scholar 

  • Haynes B, 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 

  • Hemsell DL, Grodin JM, Brenner PF, Siiteri PK, MacDonald PC. Plasma precursors of estrogen. II. Correlation of the extent of conversion of plasma androstendione to estrone with age. Journal of Clinical Endocrinology and Metabolism 38: 476–479, 1974

    Article  PubMed  CAS  Google Scholar 

  • Henderson D, Habenicht U-F, Nishino Y, El Etreby MF. Estrogens and benign prostatic hyperplasia. The basis for aromatase therapy. Steroids 50: 219–223, 1987

    Article  PubMed  CAS  Google Scholar 

  • Höffken K, Jonat W, Possinger K, Kolbel M, Kunz T, et al. Aromatase inhibition with 4-hydroxyandrostendione 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 

  • Höffken K, Kemp H, Miller AA, Miller B, Schmidt CG, et al. Aminoglutethimide without hydrocortisone in the treatment of postmenopausal patients with advanced breast cancer. Cancer Treatment Reports 70: 1153–1157, 1986

    PubMed  Google Scholar 

  • Horvath G, Stenahl U, Kalling M, Ferno M, Himmelmann A, et al. Antiestrogenic treatment of advanced and recurrent card-noma corporis uteri-A phase II study of toremifene. Anticancer Research 10: 323–326, 1990

    PubMed  CAS  Google Scholar 

  • Huggins C, Hodges CV. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer 1: 293–297, 1941

    CAS  Google Scholar 

  • James VHT, McNeill JM, Beranek PA, Bonney RC, Reed MJ. The role of tissue steroids in regulating aromatase and oestradiol 17-beta-hydroxy-steroid dehydrogenase activities in breast and endometrial cancer. Journal of Steroid Biochemistry 25: 787–790, 1986

    Article  PubMed  CAS  Google Scholar 

  • James VHT, Reed MJ, Adams EF, Ghilchik M, Lai LC, et al. Oestrogen uptake and metabolism in vivo. In Beck JS (Ed.) Estrogens and the human breast, Vol. 95, Section B, pp. 185–193, Proceedings of the Royal Society, Edinburgh, 1989

    Google Scholar 

  • Jones AL, MacNeill F, Jacobs S, Lønning PE, Powles TJ, et al. The influence of intramuscular 4 hydroxyandrostenedione on peripheral aromatisation in breast cancer patients. European Journal of Cancer 28A: 1712–1716, 1992

    Article  PubMed  CAS  Google Scholar 

  • Jordan VC. Antiestrogens for the treatment of endometrial cancer. In Schultz et al. (Eds) Endometrial Cancer, pp. 157–164, Zuckschwerdt W Verlag, 1987

  • Judd HL, Shamoniki IM, Frumar AM, Lagasse LD. Origin of serum estradiol in postmenopausal women. Obstetrics and Gynecology 59: 680–686, 1982

    PubMed  CAS  Google Scholar 

  • Kaye SB, Woods RL, Fox RM, Coates AS, Tattersall MH, et al. Use of aminoglutethimide as second-line endocrine therapy in metastatic breast cancer. Cancer Research 42 (Suppl.): 3445–3447, 1982

    Google Scholar 

  • Kissin MW, Kark AE. Irreversible thrombocytopenia following aminoglutethimide. Cancer Treatment Reports 67: 849, 1983

    PubMed  CAS  Google Scholar 

  • Klein LA. Prostatic carcinoma. New England Journal of Medicine 300: 824–833, 1979

    Article  PubMed  CAS  Google Scholar 

  • Kozak I, Bartsch W, Krieg M, Voigt KD. Nuclei of stroma: site of the highest estrogen concentration in human benign prostatic hyperplasia. Prostate 3: 433–438, 1982

    Article  PubMed  CAS  Google Scholar 

  • Krieg M, Kloetzl G, Kaufmann J, Voigt KD. Stroma of benign prostatic hyperplasia: preferential tissue for androgen and oestrogen binding. Acta Endocrinologica 96: 422–432, 1981

    PubMed  CAS  Google Scholar 

  • Kvinnsland S, Lønning PE, Dahl O. Treatment of breast cancer with aminoglutethimide. Acta Radiologica Oncology 23: 421–424, 1984

    Article  PubMed  CAS  Google Scholar 

  • Labrie F, Dupont A, Belanger A, Brochu M, Turina E, et al. Antihormone treatment for prostate cancer relapsing after treatment with flutamide and castration. British Journal of Urology 63: 634–638, 1989

    Article  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 

  • 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 

  • Loening SA, Beckley S, Brady MF, Chu TM, deKernion JB, et al. Comparison of estramustine phosphate, methothrexate and cis-platinum in patients with advanced, hormone refractory prostate cancer. Journal of Urology 129: 1001–1006, 1983

    PubMed  CAS  Google Scholar 

  • Lønning PE. Aminoglutethimide treatment of breast cancer. PhD Thesis, University of Bergen, 1989

  • Lønning PE, Dowsett M, Powles TJ. Postmenopausal estrogen synthesis and metabolism: alteration caused by aromatase inhibitors used for the treatment of breast cancer. Journal of Steroid Biochemistry 35: 335–366, 1990

    Article  Google Scholar 

  • Lønning PE, Jacobs S, Jones A, Haynes B, Powles T, Dowsett M. 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, Johannessen DC, Thorsen T. Alterations in the production rate and the metabolism of oestrone and oestrone sulfate in breast cancer patients treated with aminoglutethimide. British Journal of Cancer 60: 107–111, 1989

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Lønning PE, Kvinnsland S, Thorsen T, Ueland PM. 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, Kvinnsland S. Mechanism of action of aminoglutethimide as endocrine therapy of breast cancer. Drugs 35: 685–710, 1988

    Article  PubMed  Google Scholar 

  • Lønning PE, Kvinnsland S, Jahren G. Aminoglutethimide and warfarin: a new important drug interaction. Cancer Chemotherapy and Pharmacology 12: 10–12, 1984b

    Article  PubMed  Google Scholar 

  • Lønning PE, Skulstad P. Alterations in the urine excretion of estrogen metabolites in breast cancer women treated with aminoglutethimide. Journal of Steroid Biochemistry 33: 565–571, 1989

    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 enantiomer of warfarin in patients with breast cancer. Cancer Chemotherapy and Pharmacology 17: 177–181, 1986

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • MacAdams MR, White RH, Chipps BE. Reduction of serum testosterone levels during chronic glucocorticoid therapy. Annals of Internal Medicine 104: 648–651, 1986

    PubMed  CAS  Google Scholar 

  • Martucci CP, Fishman J. Impact of continuously administered catechol estrogens on uterine growth and luteinizing hormone secretion. Endocrinology 105: 1288–1292, 1977

    Article  Google Scholar 

  • Mason RC, Chetty U, Miller WR, Howkins RA, Forrest AP, et al. Aminoglutethimide and advanced breast cancer. Transactions Biochemical Society 8: 301, 1980

    CAS  Google Scholar 

  • McCraken M, Benson EA, Hickling P. Systemic lupus erythematosus induced by aminoglutethimide. British Medical Journal 281: 1254, 1980

    Article  PubMed  CAS  Google Scholar 

  • Murray R, Pitt P. Aminoglutethimide in tamoxifen resistant patients in the Melbourne experience. Cancer Research 42 (Suppl.): 3437–3440, 1982

    Google Scholar 

  • Murray R, Pitt P. Treatment of advanced prostatic cancer resistant to conventional therapy with aminoglutethimide. European Journal of Cancer and Clinical Oncology 21: 453–458, 1985

    Article  CAS  Google Scholar 

  • Nagel GA, Wander H-E, Blossey H-C. Phase II study of aminoglutethimide and medroxyprogesterone acetate in the treatment of patients with advanced breast cancer. Cancer Research 42 (Suppl.): 3442S–3444S, 1982

    PubMed  CAS  Google Scholar 

  • Nemoto T, Rosner D, Patel JK, Dao TL. Aminoglutethimide in patients with metastatic breast cancer. Cancer 63: 1673–1675, 1989

    Article  PubMed  CAS  Google Scholar 

  • Newsome HH, Brown PW, Terz KK, Lawrence Jr W. Medical and surgical adrenalectomy in patients with advanced breast carcinoma. Cancer 39: 543–546, 1977

    Article  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Paridaens R, Leclercq G, Heuson JC. Estrogen receptor status and the clinical response to a combination of aminoglutethimide and Cortisol in advanced breast cancer. Recent Results Cancer Research 51: 248–252, 1984

    Article  Google Scholar 

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

    CAS  Google Scholar 

  • Perrault J, Domovitch E. Aminoglutethimide and cholestasis. Annals of Internal Medicine 100: 160, 1984

    PubMed  CAS  Google Scholar 

  • Pickles T, Perry L, Murray P, 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, Perry LA, Chard T. Androgen suppression by hydrocortisone without aminoglutethimide in orchidectomised men with prostatic cancer. British Journal of Urology 59: 255–257, 1987

    Article  PubMed  CAS  Google Scholar 

  • Pollow K, Lubbert H, Bouquoi E, Kreutzer G, Pollow B. Characterization and comparison of receptors for 17beta-estradiol and progesterone in human proliferative endometrium and endometrial carcinoma. Endocrinology 96: 319–328, 1975

    Article  PubMed  CAS  Google Scholar 

  • Ponder BAJ, Shearer RJ, Pococ RD, Miller J, Easton D, et al. Response to aminoglutethimide and cortisone acetate in advanced prostatic cancer. British Journal of Cancer 50: 757–763, 1984

    Article  PubMed  CAS  Google Scholar 

  • Pronzato P, Ardizzoni A, Lionetto R, Conte P, Rosso R, et al. Aminoglutethimide as second-line endocrine treatment in metastatic breast cancer. Tumori 71: 297–300, 1985

    PubMed  CAS  Google Scholar 

  • Quinn MA, Campbell JJ, Murray R, Pepperell RJ. Tamoxifen and aminoglutethimide in the management of patients with advanced endometrial carcinoma not responsive to medroxyprogesterone. Australian and New Zealand Journal of Obstetrics and Gynaecology 21: 226–229, 1981

    Article  PubMed  CAS  Google Scholar 

  • Reed MJ, Lai LC, Owen AM, Coldham NG. 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 

  • Robinson MGR. Aminoglutethimide: medical adrenalectomy in the management of carcinoma of the prostate. A review after 6 years. British Journal of Urology 52: 328–329, 1980

    Article  PubMed  CAS  Google Scholar 

  • Robinson MRG, Shearer RJ, Fergusson JD. Adrenal suppression in the treatment of carcinoma of the prostate. British Journal of Urology 46: 555–559, 1974

    Article  PubMed  CAS  Google Scholar 

  • Rostom AY, Folkes A, Lord C, Notley RG, Schweitzer FAW, et al. Aminoglutethimide therapy for advanced carcinoma of the prostate. British Journal of Urology 54: 552–555, 1982

    Article  PubMed  CAS  Google Scholar 

  • Samojlik E, Santen RJ. Adrenal suppression with aminoglutethimide III. Comparison of plasma delta-4 and delta-5 steroids in postmenopausal women treated for breast carcinoma. Journal of Clinical Endocrinology and Metabolism 47: 717–724, 1978

    Article  PubMed  CAS  Google Scholar 

  • Samojlik E, Santen RJ, Worgul TJ. Suppression of residual oestrogen production with aminoglutethimide in women following surgical hypophysectomy or adrenalectomy. Clinical Endocrinology 20: 43–51, 1984

    Article  PubMed  CAS  Google Scholar 

  • Samojlik E, Veldhuis JD, Wells SA, Santen R. Preservation of androgen secretion during estrogen suppression with aminoglutethimide in the treatment of metastatic breast carcinoma. Journal of Clinical Investigation 65: 602–611, 1980

    Article  PubMed  CAS  Google Scholar 

  • Sanford E, Drago JR, Rohner TJ, Santen R, Lipton A. Aminogluthetimide, medical adrenalectomy for advanced prostatic carcinoma. Journal of Urology 115: 170–174, 1976

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Santen R, Samojlik E. Medical adrenalectomy for metastatic breast carcinoma. In McGuire WI (Ed.) Breast cancer, current topics, pp. 79–115, Plenum, London, 1979

    Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Santen RJ, Santner SJ, Harvey HA, Lipton A, Simmons M, et al. Marked heterogeneity of aromatase activity in human malignant melanoma tissue. European Journal of Cancer and Clinical Oncology 24: 1811–1816, 1988

    Article  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Santen RJ, Worgul TJ, Lipton A, Harvey H, Boucher AE, et al. Aminoglutethimide as treatment of postmenopausal women with advanced breast carcinoma. Annals of Internal Medicine 96: 904–1001, 1982

    Google Scholar 

  • Santen RJ, Worgul TJ, Samojlik E, Interrante A, Boucher AE, et al. A randomized trial comparing surgical adrenalectomy with aminoglutethimide plus hydrocortisone in women with advanced breast cancer. New England Journal of Medicine 308: 545–551, 1981

    Article  Google Scholar 

  • Santner SJ, Feil PD, Santen RJ. In situ estrogen production via the estrone sulfate pathway in breast tumours: relative importance versus the aromatase pathway. Journal of Clinical Endocrinology and Metabolism 59: 29–33, 1984

    Article  PubMed  CAS  Google Scholar 

  • Santner SJ, Leszczynski, Wright C, Manni A, Feil D. Estrone sulfate: a potential source of estradiol in human breast cancer tissue. Breast Cancer Research and Treatment 7: 35–44, 1986

    Article  PubMed  CAS  Google Scholar 

  • Schmidt JD, Scott WW, Gibbons R, Johnson E, Prout GR, et al. Chemotherapy programs of the National Prostatic Cancer Project (NPCP). Cancer 45: 1937–1946, 1980

    PubMed  CAS  Google Scholar 

  • Schoonees R, Schaklch DS, Reynoso G, Murphy GP. Bilateral adrenalectomy for advanced prostatic carcinoma. Journal of Urology 108: 123–125, 1972

    PubMed  CAS  Google Scholar 

  • Schwarzel WC, Kruggel WG, Brodie H. Studies on the mechanism of estrogen biosynthesis. VIII. The development of inhibitors of the enzyme system in human placenta. Endocrinology 98: 866–880, 1973

    Article  Google Scholar 

  • Schweikert HU, Milewich L, Wilson J. Aromatization of androstendione by cultured human fibroblasts. Journal of Clinical Endocrinology and Metabolism 43: 785–795, 1976

    Article  PubMed  CAS  Google Scholar 

  • Scott WW, Meiron M, Walsh PC. Hormonal therapy of prostatic cancer. Cancer 45: 1929–1936, 1980

    PubMed  CAS  Google Scholar 

  • Shand DG. Biological determinants of altered pharmacokinetics in the elderly. Gerontology 28(Suppl. 1): 8–17, 1982

    Article  PubMed  CAS  Google Scholar 

  • Shearer RJ, Davies JH, Dowsett M, Malone PR, Hedley A, et al. Aromatase inhibition in advanced prostatic cancer: preliminary communication. British Journal of Cancer 62: 275–276, 1990

    Article  PubMed  CAS  Google Scholar 

  • Shearer, RJ, Hendry WF, Sommerville IF, Ferguson JD. Plasma testosterone. An accurate monitor of hormone treatment in prostatic cancer. British Journal of Urology 45: 668–677, 1973

    Article  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 

  • Steele RE, Mellor L, Sawyer WK, Wasvary JM, Brown 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 

  • Stuart-Harris R, Dowsett M, Bozek T, McKinna, Gazet JC, et al. Low dose aminoglutethimide in treatment of breast cancer. Lancet 2: 604–607, 1984

    Article  PubMed  CAS  Google Scholar 

  • Stuart-Harris R, Dowsett M, D’Souza A, Donaldson A, Harris A. Endocrine effects of low dose aminoglutethimide as an aromatase inhibitor in the treatment of breast cancer. Clinical Endocrinology 22: 219–226, 1985

    Article  PubMed  CAS  Google Scholar 

  • Troner MB. Aminoglutethimide in the treatment of metastatic breast cancer. Cancer Research 42 (Suppl.): 3401–3494, 1982

    Google Scholar 

  • van Landeghem AAJ, Poortman J, Nabuurs M, Thyssen JHH. Endogenous concentration and subcellular distribution of estrogens in normal and malignant human breast tissue. Cancer Research 45: 2900–2906, 1985

    PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Vermeulen A, Paridaens R, Hensen JC. Effects of Aminoglutethimide on adrenal steroid secretion. Clinical Endocrinology 19: 673–678, 1983

    Article  PubMed  CAS  Google Scholar 

  • Vermeulen A, Deslypere JP, Paridaens R, Leclercq G, Roy F, et al. Aromatase, 17 beta-hydroxysteroid dehydrogenase and intratissular sex hormone concentrations in cancerous and normal glandular breast tissue in postmenopausal women. European Journal of Cancer and Clinical Oncology 22: 515–525, 1986

    Article  CAS  Google Scholar 

  • Vermeulen A, Rubens R, Verdonck L. Testosterone secretion and Metabolism in male senescence. Journal Clinical Endocrinology and Metabolism 34: 730–735, 1972

    Article  CAS  Google Scholar 

  • Vincent MD, Clink HM, Coombes RC, Smith IE, Kandier R, et al. Aminoglutethimide (with hydrocortisone) induced agranulocytosis in primary breast cancer. British Medical Journal 291: 105–106, 1985

    Article  PubMed  CAS  Google Scholar 

  • Volk H, Deupree RH, Goldenberg IS, Wilde RC, Carabas RA, et al. A dose response evaluation of delta-1-testolactone in advanced breast cancer. Cancer 33: 9–13, 1974

    Article  PubMed  CAS  Google Scholar 

  • Wilkinson GR, Shand DG. Commentary: a physical approach to hepatic drug clearance. Clinical Pharmacology and Therapeutics 18: 377–390, 1975

    PubMed  CAS  Google Scholar 

  • Withmore WF. The natural history of prostatic carcinoma. Cancer 32: 1104–1112, 1973

    Article  Google Scholar 

  • Worgul TJ, Santen RJ, Samojlik E, Veldhus J, Lipton A, et al. Clinical and biochemical effect of aminogluthetimide in the treatment of advanced prostatic carcinoma. Journal of Urology 129: 51–55, 1983

    PubMed  CAS  Google Scholar 

  • Wouters W, De Coster R, Tuman RW, Bowden CR, Bruynseels J, et al. Aromatase inhibition by R 76713: experimental and clinical pharmacology. Journal of Steroid Biochemistry 34: 427–430, 1989

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Therapeutic Oncology and Radiophysics, Haukeland Sykehus, University Hospital of Bergen, Bergen, Norway

    D. C. Johannessen &  P. E. Lønning

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Johannessen, D.C., Lønning, P.E. Aromatase Inhibitors in Malignant Diseases of Aging. Drug & Aging 2, 530–545 (1992). https://doi.org/10.2165/00002512-199202060-00008

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