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Can Megestrol Acetate Induce Thrombosis in Advanced Oncology Patients Receiving Chemotherapy?

  • Ordu, Cetin (Department of Medical Oncology, Faculty of Medicine, Bilim University) ;
  • Pilanci, Kezban Nur (Department of Medical Oncology, Faculty of Medicine, Bilim University) ;
  • Koksal, Ulkuhan Iner (Department of Medical Oncology, Faculty of Medicine, Bilim University) ;
  • Okutur, Kerem (Department of Medical Oncology, Faculty of Medicine, Bilim University) ;
  • Saglam, Sezer (Department of Medical Oncology, Faculty of Medicine, Bilim University) ;
  • Tecimer, Coskun (Department of Medical Oncology, Faculty of Medicine, Bilim University) ;
  • Demir, Gokhan (Department of Medical Oncology, Faculty of Medicine, Bilim University)
  • Published : 2015.01.06

Abstract

Background: Megestrol acetate (MA) is a steroid origin medicine often used for control of cachexia in oncologic palliative care. Thrombosis is a common problem in oncology patients. One question is whether MA can cause thrombosis. This retrospective, registry-based analysis was therefore conducted to assess thrombotic processes in oncology patients using MA concurrent with chemotherapy. Materials and Methods: Data on oncology patients at the metastatic stage using MA were obtained from the archives of our center. Outcomes of patients were evaluated for thromboembolic events (VTEs) during treatment. Results: Ninety-seven oncology patients with a median age of 62 (33-84) years were included. During the median follow-up of 17 months, 58 (59.8%) died leaving 39 (31.2%) still alive. Median overall survival (OS) was 19 months (6-180). Mean time of MA use was 8.69 months(${\pm}3.53$), with a median dose of 160mg (range 160-480mg). Eleven VTEs were detected after MA use, 4 of these in pancreatic cancer cases. The patients with thrombosis non-significantly had worse OS, than those without thrombosis (p=0.106). Conclusions: This trial revealed that the 11.3% of all patients developed thrombosis,who had been treated with MA and chemotherapy concomittantly. There was no statistically significant difference regarding to occurrence of thrombotic process, among the patients receiving different chemotherapy regimens with MA concomittantly. Pancreatic cancer seemed to be related to thrombosis rather than MA use.

Keywords

References

  1. Abrams JS, Cirrincione C, Aisner J, et al (1992). A phase III doseresponsetrial of megestrol acetate (MA) in metastatic breast cancer. Proc Am Soc Clin Oncol, 11, 56.
  2. Aleem A, Al Diab AR, Alsaleh K, et al (2012). Frequency, clinical pattern and outcome of thrombosis in cancer patients in Saudi Arabia. Asian Pac J Cancer Prev, 13, 1311-5. https://doi.org/10.7314/APJCP.2012.13.4.1311
  3. Berenstein EG, Ortiz Z (2005). Megestrol acetate for the treatment of anorexia-cachexia syndrome. Cochrane Database Syst Rev, 13, CD004316.
  4. LaMarr B, Crawford R (2012).Venous thromboembolism and weight changes in veteran patients using megestrol acetate as an appetite stimulant. Federal practitioner, 10, 31-5.
  5. Blom JW, Doggen CJ, Osanto S, Rosendaal FR (2005). Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA, 293, 715-22. https://doi.org/10.1001/jama.293.6.715
  6. Blom JW, Vanderschoot JP, Oostindier MJ, et al (2006). Incidence of venous thrombosis in a large cohort of 66,329 cancer patients: Results of a record linkage study. J ThrombHaemost, 4, 529-35. https://doi.org/10.1111/j.1538-7836.2006.01804.x
  7. Bolen JC, Andersen RE, Bennett RG (2000). Deep vein thrombosis as a complication of megestrol acetate therapy among nursing home residents. J Am Med Dir Assoc, 1, 248-52.
  8. Bruera E, Macmillan K, Kuehn N, et al (1990). A controlled trial of megestrol acetate on appetite, caloric intake, nutritional status, and other symptoms in patients with advanced cancer. Cancer, 66, 1279-82. https://doi.org/10.1002/1097-0142(19900915)66:6<1279::AID-CNCR2820660630>3.0.CO;2-R
  9. Bruera E, Ernst S, Hagen N, et al (1996). Symptomatic effects of megestrol acetate (MA): A double-blind, crossover study. Proc Am Soc Clin Oncol, 15, 531.
  10. Chew HK, Wun T, Harvey D, et al (2006). Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch Intern Med, 166, 458-64. https://doi.org/10.1001/archinte.166.4.458
  11. Chen C, Li G, Liu YD, Gu YJ (2014). A new D-dimer cutoff value to improve the exclusion of deep vein thrombosis in cancer patients. Asian Pac J Cancer Prev, 15, 1655-8. https://doi.org/10.7314/APJCP.2014.15.4.1655
  12. Cruz JM, Muss HG, Brockschmidt JK, et al (1990). Weight changesin women with metastatic breast cancer treated with megestrol acetate: A comparison of standard versus highdose therapy. Semin Oncol1, 7, 63-7.
  13. Desport JC, Blanc-Vincent MP, Delabaere G, et al (2000). Standard, options, recommendations (SOR) pour l'utilisation des medicaments orexige nes en cance rologie. Bull Cancer, 87, 315-28.
  14. Heit JA (2008). The epidemiology of venous thromboembolism in the community. Arterioscler Thromb Vasc Biol, 28, 370-2. https://doi.org/10.1161/ATVBAHA.108.162545
  15. Heit JA, Silverstein MD, Mohr DN, et al (2000). Risk factors for deepvein thrombosis and pulmonary embolism: A population-based case-control study. Arch Intern Med, 160, 809-15. https://doi.org/10.1001/archinte.160.6.809
  16. Khorana AA (2010). Venous thromboembolism and prognosis in cancer. Thromb Res, 125, 490-3. https://doi.org/10.1016/j.thromres.2009.12.023
  17. Khorana AA (2012). Cancer-associated thrombosis: updates and controversies. Hematology Am Soc Hematol Educ Program, 2012, 626-30.
  18. Khorana AA, Dalal M, Lin J, Connolly GC (2013). Incidence and predictors of venous thromboembolism (VTE) among ambulatory high-risk cancer patients undergoing chemotherapy in the United States. Cancer, 119, 648. https://doi.org/10.1002/cncr.27772
  19. Khorana AA, Francis CW, Culakova E, Lyman GH (2005). Risk factors for chemotherapy-associated venous thromboembolism in a prospective observational study. Cancer, 104, 2822. https://doi.org/10.1002/cncr.21496
  20. Kuderer NM, Ortel TL, Francis CW (2009). Impact of venous thromboembolism and anticoagulation on cancer and cancer survival. J Clin Oncol, 27, 4902-11. https://doi.org/10.1200/JCO.2009.22.4584
  21. Loprinzi CL, Ellison NM, Schaid DJ, et al (1990). Controlled trial of megestrol acetate for the treatment of cancer anorexia and cachexia. J Natl Cancer Inst, 82, 1127-32. https://doi.org/10.1093/jnci/82.13.1127
  22. Loprinzi CL, Michalak JC, Schaid DJ, et al (1993). Phase III evaluation of four doses of megestrol acetate as therapy for patients with canceranorexia and/or cachexia. J Clin Oncol, 11, 762-67.
  23. Mandala M, Falanga A, Roila F (2011). Management of venous thromboembolism (VTE) in cancer patients: ESMO clinical practice guidelines. Ann Oncol, 22, 85-92.
  24. Maltoni M, Nanni O, Scarpi E, et al (2001). High-dose progestins for the treatment of cancer anorexia-cachexia syndrome: A systematic review of randomised clinical trials. Ann Oncol, 12, 289-300. https://doi.org/10.1023/A:1011156811739
  25. Megace [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2012.
  26. McCarthy HD, Crowder RE, Dryden S, Williams G (1994). Megestrol acetate stimulates food and water intake in the rat: effects on regional hypothalamic neuropeptide Y concentrations. Eur J Pharmacol, 265, 99-102. https://doi.org/10.1016/0014-2999(94)90229-1
  27. Morley J, Thomas DR, Wilson MM (2006). Cachexia: pathophysiology and clinical relevance. Am J Clin Nutr, 83, 735-43.
  28. Norleena P. Gullett, Vera Mazurak, Gautam Hepbar, Thomas R. Ziegler (2012). Nutritional interventions for cancer-induced cachexia. Curr Probl Cancer, 35, 58-90.
  29. Oberhoff C, Hoffmann O, Winkler UH, Schindler AE (2001). Hemostatic effects of high-dose megestrol acetate therapy in patients with advanced gynecological cancer. Gynecol Endocrinol, 15, 341-8. https://doi.org/10.1080/gye.15.5.341.348
  30. Otten HM, Mathijssen J, Ten Cate H, et al (2004). Symptomatic venous thromboembolism in cancer patients treated with chemotherapy: an underestimated phenomenon. Arch Intern Med, 164, 190-4. https://doi.org/10.1001/archinte.164.2.190
  31. Parnes HL, Conaway M, Aisner J, et al (1999). Megestrol acetate for the treatment of cachexia in patients with advanced lung or colorectal cancers. Cancer Ther, 2, 75-82.
  32. Ruiz Garcia V, Lopez-Briz E, Carbonell Sanchis R, et al (2013). Megestrol acetate for treatment of anorexia-cachexia syndrome (Review). Cochrane Database Syst Rev, 3, CD004310.
  33. Seng S, Liu Z, Chiu SK, et al (2012). Risk of venous thromboembolism in patientswith cancer treated with cisplatin: A systematic review and meta-analysis. J Clin Oncol, 30, 4416-26. https://doi.org/10.1200/JCO.2012.42.4358
  34. Seddighzadeh A, Shetty R, Goldhaber SZ (2007). Venous thromboembolism in patients with active cancer. Thromb Haemost, 98, 656-61.
  35. Sorensen HT, Mellemkjaer L, Olsen JH, et al (2000). Prognosis of cancers associated with venous thromboembolism. N Engl J Med, 34, 1846-50.
  36. Tchekmedyian NS, Hickman M (1992). Megestrol acetate in cancer anorexia and weight loss. Cancer, 69, 1268-74.
  37. Tchekmedyian NS, Hickman M, Siau J, et al (1991). Treatment of cancer anorexia with megestrol acetate: Impact on quality of life. Oncology, 5, 119-26.
  38. Topkan E, Yavuz AA, Ozyilkan O (2007). Cancer cachexia: pathophysiologic aspects and treatment options. Asian Pac J Cancer Prev, 8, 445-51.
  39. Zhan P, Wang Q, Qian Q, Yu LK (2013). Megestrol acetate in cancer patients with anorexia-cachexia syndrome: a metaanalysis. Transl Cancer Res, 2, 74-9.

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