1. High-dose progestins for the treatment of cancer anorexia - cachexia syndrome 主講人 : 徐嫈惠 2008/01/29

4.   Anorexia — defined as the loss of the desire to eat. — several factors are involved in its pathogenesis and, once developed, anorexia affects the clinical course of the underlying disease.

5. Pathogenetic mechanisms of anorexia-cachexia Several factors are considered to be putative mediators of cancer anorexia, including hormones (eg, leptin), neuropeptides (eg, neuropeptide Y), cytokines (eg, interleukin 1 and 6, and tumour necrosis factor), and neurotransmitters (eg, serotonin).

6. Pathogenetic mechanisms of anorexia-cachexia

8. Medroxyprogesterone acetate  簡介 Medroxyprogesterone acetate(MPA) 是由黃體激素 Medroxyprogesterone acetate(MPA) 是由黃體激素 (17-OH-progesterone) 衍生而來，是一種合成類固醇， (17-OH-progesterone) 衍生而來，是一種合成類固醇， 口服給藥，結構與天然的黃體激素相似，不同處在 α-6 位置 口服給藥，結構與天然的黃體激素相似，不同處在 α-6 位置 有 Methyl group 與 17 位置有 acetoxy group 。 有 Methyl group 與 17 位置有 acetoxy group 。

9. Medroxyprogesterone acetate  衛生署適應症 1. 不能手術及復發性或轉移性之子宮內膜癌 1. 不能手術及復發性或轉移性之子宮內膜癌 2. 停經後婦女之乳癌 2. 停經後婦女之乳癌 3. 攝護腺癌 3. 攝護腺癌 4. 伴有惡病質 (cachexia) 之末期癌症 4. 伴有惡病質 (cachexia) 之末期癌症  劑量與用法 1. 伴有惡病體質之末期癌症：每天 1000mg ，可一次服用或是分為每天 2 次 服用。 1. 伴有惡病體質之末期癌症：每天 1000mg ，可一次服用或是分為每天 2 次 服用。 2. 每日可從 100~1000 mg （高劑量時可分為每天 2~3 次服用），一般低劑量 用於子宮內膜癌，高劑量用於末期的轉移性乳癌。 2. 每日可從 100~1000 mg （高劑量時可分為每天 2~3 次服用），一般低劑量 用於子宮內膜癌，高劑量用於末期的轉移性乳癌。 晚期和轉移性乳癌 : 1000 mg/day 。 晚期和轉移性乳癌 : 1000 mg/day 。 晚期和轉移性子宮內膜癌 : 500 mg/day 晚期和轉移性子宮內膜癌 : 500 mg/day 晚期和轉移性攝護腺癌 : 500 mg/day 。 晚期和轉移性攝護腺癌 : 500 mg/day 。

10. Non-FDA Labeled Indications Non-FDA Labeled Indications Loss of appitite a) Overview: FDA Approval: Adult, no; Pediatric, no Efficacy: Adult, Evidence favors efficacy. Efficacy: Adult, Evidence favors efficacy. b) summary: Medroxyprogestrone has been shown to be effective. c) Adult: Medroxyprogesterone helped improve appetite and prevent further weight loss in cancer patients who were losing weight but not yet cachectic. Patients with advanced-stage, incurable, non-hormone sensitive cancer were given either medroxyprogesterone 500 mg twice daily or placebo. At 12 weeks a statistically significant difference of 2 kg was seen between the two groups (p=0.04). Further studies are needed to verify these results. (Simons et al, 1996). (Simons et al, 1996).

11. Drug therapy   Progestagens ( medroxyprogesterone acetate) are the first-line therapy for cancer anorexia.   Medroxyprogesterone has been shown to increase appetite and food intake with stabilization of body weight at a dose of 1000 mg (500 mg twice).   Their prophagic effect seems to be mediated by the downregulation of the synthesis and release of cytokines leading to an increase in hypothalamic concentrations of neuropeptide Y. CA Cancer J Clin 2002;52:72-91

12. Problem and Discussion  Q. 醫師開立 Medroxyprogestrone(500mg/tab.)1#QD 是否 合理？   A. Medroxyprogesterone has been shown to increase appetite and food intake with stabilization of body weight at a dose of 1000 mg (500 mg twice). THE LANCET Oncology Vol 4 November 2003

13. Conclusion   Cancer anorexia is a syndrome that can be effectively treated. However, it is not known whether amelioration of anorexia and improvements in energy intake would result in a long-term benefit for patients with cancer in terms of reduced morbidity and mortality. THE LANCET Oncology Vol 4 November 2003   The authors conclude that MPA is able to stimulate increased food intake significantly and to reverse fat loss concomitantly in patients with non-hormone-sensitive cancer. Cancer 1998;82:553–60.

14. 補充資料

15. The Comparison of Farlutal and Megaplex Megaplex Farlutal Megaplex Farlutal

16. The Comparison of Farlutal and Megaplex   The mechanism of action of progestational drugs: 1. It may stimulate appetite via neuropeptide Y in the CNS. 2. It may down-regulating the synthesis and release of proinflammatory cytokines, e.g., TNF-a, IL-1, IL-6. proinflammatory cytokines, e.g., TNF-a, IL-1, IL-6. CA Cancer J Clin 2002;52:72-91

17. The Comparison of Farlutal and Megaplex  The Dosage  The Dosage of progestational drugs: Farlutal: 1. Dosage: range from 500 mg/day to 4000 mg/day. 1. Dosage: range from 500 mg/day to 4000 mg/day. 2. 1000 mg/day was reported improvement of appetite and 2. 1000 mg/day was reported improvement of appetite and body weight. body weight. Megaplex: Megaplex: 1. Dosages: range from 160 mg/day of megestrol to 800 mg/day. 2. It is recommended that a patient be started on the lowest dosage (160 mg/day) and the dose be titrated upwards according to the clinical response. CA Cancer J Clin 2002;52:72-91

18. The Comparison of Farlutal and Megaplex  The side effect  The side effect of progestational drugs: 1. Both megestrol and medroxyprogesterone can induce thromboembolic phenomena,breakthrough uterine bleeding, peripheral edema, hyperglycemia, hypertension, adrenal suppression, and adrenal insufficiency (if the drug is abruptly discontinued). CA Cancer J Clin 2002;52:72-91