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A phase I/II study of high-dose megestrol acetate in the treatment of metastatic breast cancer

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Summary

A dose-response relationship has been suggested for medroxyprogesterone acetate in the treatment of advanced breast cancer. To determine the tolerability and efficacy of increasing doses of megestrol acetate in the treatment of metastatic breast cancer, we conducted a phase I/II study among 57 patients. Three patients each received 480,800, and 1280 mg/d; 48 patients received 1600 mg/d. Of the 57 patients, 56 patients had had disease progression on prior hormone therapy, chemotherapy, or both. Twenty-seven patients had previously received standard-dose MA (160 mg/d). Among the 37 patients with measurable disease, high-dose megestrol acetate (HDMA) produced 6 (16%) complete responses (CRs) and 6 (16%) partial responses (PRs); 11 patients achieved stable disease (SD). HDMA resulted in improvement or stabilization in 12 of the 20 patients with evaluable, non-measurable disease. There were no responses among the 6 patients with liver metastases. Among the 27 patients who were previously treated with standard-dose MA, including 9 patients with primary treatment failure, HDMA resulted in 1 CR, 3 PRs, and 10 SD. Toxicities, which were mild and reversible, included fluid retention, hypertension, hyperglycemia, and mild congestive heart failure. Two patients had superficial phlebitis. The most profound side effect was weight gain which occurred in 43 patients (75%). This study suggests a dose-response relationship for MA in the treatment of advanced breast cancer. A randomized trial to determine the optimal dose is ongoing.

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References

  1. Beatson GT: On the treatment of inoperable cases of carcinoma of the mamma: Suggestions for a new method of treatment with illustrative cases. Lancet ii: 104–107, 1896

    Google Scholar 

  2. Haller DG, Glick JH: Progestational agents in advanced breast cancer: An overview. Semin Oncol 13: 2–8, 1986

    Google Scholar 

  3. Goldenberg IS: Clinical trial of 'E-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

    Google Scholar 

  4. Hedley D, Dalgeish A, Raghavan D, Tattersall MH, Coates A, Fox R: Advanced breast cancer: Response to high dose oral medroxyprogesterone acetate. Aust NZ J Med 14: 251–254, 1984

    Google Scholar 

  5. Hortobagyi GN, Buzdar AU, Frye D, Yap HY, Hug V, Pinnamaneni K, Fraschini G, Halvorson HC, Blumenschein GR: Oral medroxyprogesterone acetate in the treatment of metastatic breast cancer. Breast Cancer Res Treat 5: 321–326, 1985

    Google Scholar 

  6. Izuo M, Iino Y, Tominaga T, Nomura Y, Abe O, Enomoto K, Takatani O, Kubo K: Oral high-dose medroxyprogesterone acetate therapy in advanced breast cancer: clinical and endocrine studies. Int Congr Series 611: 250–263, 1982

    Google Scholar 

  7. Pannuti F, Martoni A, Fruet F: Oral high-dose medroxyprogesterone acetate versus tamoxifen in postmenopausal patients with advanced breast cancer. In: Iacobelli S, Lippman ME, Della Cuna GR (eds) The Role of Tamoxifen in Breast Cancer. Raven Press, New York, 1982, pp 85–92

    Google Scholar 

  8. Cavalli F, Goldhirsch A, Jungi F, Martz G, Mermillod B, Alberto P, for the Swiss Group for Clinical Cancer Research: Randomized trial of low- versus high-dose medroxyprogesterone acetate in the induction treatment of post-menopausal patients with advanced breast cancer. J Clin Oncology 2: 414–419, 1984

    Google Scholar 

  9. Cuna GR, Calciati A, Strada MR, Bumma C, Campio L: High dose medroxyprogesterone acetate (MPA) treatment in metastatic carcinoma of the breast: a dose-response evaluation. Tumori 64: 143–149, 1978

    Google Scholar 

  10. Mattsson W: High-dose medroxyprogesterone acetate treatment in advanced mammary carcinoma: A phase II investigation. Acta Radiol Oncol 17: 387–400, 1978

    Google Scholar 

  11. De Lena M, Brambilla C, Valagussa P, Bonadonna G: High-dose medroxyprogesterone acetate in breast cancer resistant to endocrine and cytotoxic therapy. Cancer Chemother Pharmacol 2: 175–180, 1979

    Google Scholar 

  12. Pannuti F, Martoni A, Di Marco AR, Piana E, Saccani F, Becchi G, Mattioli G, Barbanti F, Marra GA, Persiani W, Cacciari L, Spagnolo F, Palenzona D, Rocchetta G: Prospective, randomized clinical trial of two different high dosages of medroxyprogesterone acetate in the treatment of metastatic breast cancer. Eur J Cancer 15: 593–601, 1979

    Google Scholar 

  13. Martin F, Adlercreutz H: Aspects of megestrol acetate and medroxyprogesterone acetate metabolism. In: Garattini S, Brendes HW (eds): Pharmacology of Steroid Contraceptive Drugs. Raven, New York, 1977, pp 99–115

    Google Scholar 

  14. Ross MB, Buzdar AU, Blumenstein GR: Treatment of advanced breast cancer with megestrol acetate after therapy with tamoxifen. Cancer 49: 413–417, 1982

    Google Scholar 

  15. Alexieva-Figusch J, Van Gilse HA, Hop WC, Phoa CH, Wijst JB, Treurniet RE: Progestin therapy in advanced breast cancer: Megestrol acetate — An evaluation of 160 treated cases. Cancer 46: 2369–2372, 1980

    Google Scholar 

  16. Ansield FJ, Kallas GJ, Singson JP: Clinical results with megestrol acetate in patients with advanced carcinoma of the breast. Surg Gynecol Obstet 155: 888–890, 1982

    Google Scholar 

  17. Bonomi P, Johnson P, Anderson K, Wolter J, Bunting N, Strauss A, Roseman D, Shorey W, Economou S: Primary hormonal therapy of advanced breast cancer with megestrol acetate: predictive value of estrogen receptor and progesterone receptor levels. Semin Oncol 12: 48–54, 1985

    Google Scholar 

  18. Gregory EJ, Cohen SC, Oines DW, Mims CH: Megestrol acetate therapy for advanced breast cancer. J Clin Oncol 3: 155–160, 1985

    Google Scholar 

  19. Carpenter JT Jr, Peterson L: Use of megestrol acetate in advanced breast cancer on a single-daily-dose schedule. Semin Oncol 12: 40–42, 1985

    Google Scholar 

  20. Johnson PA, Bonomi PD, Anderson KM, Wolter JM, Economou SG: Megestrol acetate: First-line therapy for advanced breast cancer. Semin Oncol 13: 1519, 1986

    Google Scholar 

  21. Allegra JC, Bertino J, Bonomi P, Byrne P, Carpenter J, Catalano R, Creech R, Dana B, Durivage H, Einhorn L, Ettinger D, Greco FA, Greenwald E, Henderson I, Holmes F, Kinzbrunner B, Luedke S, Muss H, Nimeh N, Talley R, Wampler G, Weinreb N, Weisberg J, Wheeler R, Wiernik P: Metastatic breast cancer: Preliminary results with oral hormonal therapy. Semin Oncol 12: 61–64, 1985

    Google Scholar 

  22. Ettinger DS, Allegra J, Bertino JR, Bonomi P, Browder H, Byrne P, Carpenter J, Catalano R, Creech R, Dana B, Durivage H, Einhorn L, Greco FA, Greenwald E, Henderson I, Holmes F, Keller J, Kinzbrunner B, Losada M, Luedke S, Muss H, Nimeh N, Wampler G, Weinreb N, Weisberg J, Wheeler R, Wiernik PH: Megestrol acetate v tamoxifen in advanced breast cancer: correlation of hormone receptors and response. Semin Oncol 13: 9–14, 1986

    Google Scholar 

  23. Ingle JN, Ahmann D, Green SJ, Edmonson JH, Creagan ET, Hahn RC, Rubin J: Randomized clinical trial of megestrol acetate versus tamoxifen in paramenopausal or castrated women with advanced breast cancer. Am J Clin Oncol (CCT) 5: 155–160, 1982

    Google Scholar 

  24. Morgan LR: Megestrol acetate v tamoxifen in advanced breast cancer in postmenopausal patients. Semin Oncol 12: 43–47, 1985

    Google Scholar 

  25. Muss HB, Paschold EH, Black WR, Cooper MR, Capizzi RL, Christian R, Cruz JM, Jackson DV, Stuart JJ, Richards HF, White DR, Zekan PJ, Spurr CL, Pope E, Case D, Morgan T, Wells HB: Megestrol acetate v tamoxifen in advanced breast cancer: A phase III trial of the Piedmont Oncology association (POA). Semin Oncol 12: 55–61, 1985

    Google Scholar 

  26. Muss H, Case D, Cates-Wilkie S, Read S, Bearden J, Callahan R, Capizzi R, Cooper M, Cruz J, Jackson D, Powell B, Richards F, Spurr C, White D, Zekan P: High vs. standard dose oral progestin therapy (Megestrol Acetate) for metastatic breast cancer: A phase III trial of the Piedmont Oncologic Association (abstract). Proc Am Soc Clin Oncol 8: 22, 1989

    Google Scholar 

  27. Tchekmedyian NS, Tait N, Moody M, Aisner J: High-dose megestrol acetate: A possible treatment for cachexia. JAMA 257: 1195–1198, 1987

    Google Scholar 

  28. Alexieva-Figusch J, Blankenstein MA, Hop WCJ, Klijn JGM, Lamberts SWJ, De Jong FH, Doctor R, Adlercreutz H, Van Gilse HA: Treatment of metastatic breast cancer patients with different dosages of megestrol acetate; dose relations, metabolic and endocrine effects. Eur J Cancer Clin Oncol 20: 33–40, 1984

    Google Scholar 

  29. Grossman SA, Burch PA: Quantitation of tumor response to anti-neoplastic therapy. Semin Oncol 15: 441–454, 1988

    Google Scholar 

  30. Parnes H, Tait N, Aisner J: The potential of megestrol acetate in the treatment of cancer cachexia. Nutrition 5: 206–207, 1989

    Google Scholar 

  31. Von Roenn JH, Murphy RL, Weber KM, Williams LM, Weitzman SA: Megestrol acetate for treatment of cachexia associated with human immunodeficiency virus (HIV) infection. Ann Int Med 109: 840–841, 1988

    Google Scholar 

  32. Allegra JC, Kiefer SM: Mechanisms of action of progestational agents. Semin Oncol 12: 3–5, 1985

    Google Scholar 

  33. Blossey HC, Wander HE, Koebberling J, Nagel GA: Pharmacokinetic and pharmacodynamic basis for the treatment of metastic breast cancer with high-dose medroxyprogesterone acetate. Cancer 54: 1208–1215, 1984

    Google Scholar 

  34. Sutherland RL, Clarke CL: Progestin effects on cellular proliferation and the expression of growth factor and steroid hormone receptor genes in human breast cancer cells. Cancer Res 49: 7176–7179, 1989

    Google Scholar 

  35. CALGB 8741: A Dose Response Trial of Megestrol Acetate in Advanced Breast Cancer: A Phase III Study.

  36. CALGB 8971: A Dose Response Trial of Megestrol Acetate for the Treatment of Cachexia in Patients with Lung or Colorectal Cancer.

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Authors and Affiliations

  1. 1040 Elm Avenue, Suite 300, Long Beach, California, USA

    N. Simon Tchekmedyian

  2. University of Maryland Cancer Center, University of Maryland Hospital, 22 S. Greene Street, 21201, Baltimore, Maryland, USA

    Howard L. Parnes, Jeffrey S. Abrams, Nancy Tait & Joseph Aisner

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  1. Howard L. Parnes
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  2. Jeffrey S. Abrams
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  3. N. Simon Tchekmedyian
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  4. Nancy Tait
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  5. Joseph Aisner
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Parnes, H.L., Abrams, J.S., Simon Tchekmedyian, N. et al. A phase I/II study of high-dose megestrol acetate in the treatment of metastatic breast cancer. Breast Cancer Res Tr 18, 171–177 (1991). https://doi.org/10.1007/BF01990033

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