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

High-dose progestins for the High-dose progestins for the treatment of cancer anorexia treatment of cancer anorexia

- cachexia syndrome- cachexia syndrome

主講人主講人 :: 徐嫈惠徐嫈惠2008/01/292008/01/29

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.

Pathogenetic mechanisms of anorexia-cachexiaPathogenetic 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, andtumour necrosis factor), and neurotransmitters (eg, serotonin).



Medroxyprogesterone acetateMedroxyprogesterone acetate

簡介簡介 Medroxyprogesterone acetate(MPA)Medroxyprogesterone acetate(MPA) 是由黃體激素是由黃體激素 (17-OH-progesterone)(17-OH-progesterone) 衍生而來，是一種合成類固醇，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，不同處在口服給藥，結構與天然的黃體激素相似，不同處在 α-6α-6 位置位置有有 Methyl groupMethyl group 與與 1717 位置有位置有 acetoxy groupacetoxy group 。。　　

Medroxyprogesterone acetateMedroxyprogesterone acetate

衛生署適應症衛生署適應症 1.1. 不能手術及復發性或轉移性之子宮內膜癌不能手術及復發性或轉移性之子宮內膜癌 2.2. 停經後婦女之乳癌停經後婦女之乳癌 3.3. 攝護腺癌攝護腺癌 4.4. 伴有惡病質伴有惡病質 (cachexia)(cachexia) 之末期癌症之末期癌症劑量與用法劑量與用法 1.1. 伴有惡病體質之末期癌症：每天伴有惡病體質之末期癌症：每天 1000mg1000mg ，可一次服用或是分為每天，可一次服用或是分為每天 22 次次

服用。服用。 2.2. 每日可從每日可從 100~1000 mg100~1000 mg （高劑量時可分為每天（高劑量時可分為每天 2~32~3 次服用），一般低劑次服用），一般低劑

量量用於子宮內膜癌，高劑量用於末期的轉移性乳癌。用於子宮內膜癌，高劑量用於末期的轉移性乳癌。

晚期和轉移性乳癌晚期和轉移性乳癌 : 1000 mg/day: 1000 mg/day 。。

晚期和轉移性子宮內膜癌晚期和轉移性子宮內膜癌 : 500 mg/day : 500 mg/day 晚期和轉移性攝護腺癌晚期和轉移性攝護腺癌 : 500 mg/day: 500 mg/day 。。

Non-FDA Labeled IndicationsNon-FDA Labeled Indications Loss of appititeLoss of appitite

a) a) Overview: FDA Approval: Adult, no; Pediatric, noOverview: FDA Approval: Adult, no; Pediatric, no Efficacy: Adult, Evidence favors efficacy .Efficacy: Adult, Evidence favors efficacy .b) b) summary: Medroxyprogestrone has been shown to be effective.summary: Medroxyprogestrone has been shown to be effective.

c) c) Adult:Adult: Medroxyprogesterone helped improve appetite and prevent further Medroxyprogesterone helped improve appetite and prevent further weight loss in cancer patients who were losing weight but not yet weight loss in cancer patients who were losing weight but not yet cachectic. Patients with advanced-stage, incurable, non-hormone cachectic. Patients with advanced-stage, incurable, non-hormone sensitive cancer were given either medroxyprogesterone 500 mg sensitive cancer were given either medroxyprogesterone 500 mg twice daily or placebo. At 12 weeks a statistically significant twice daily or placebo. At 12 weeks a statistically significant difference of 2 kg was seen between the two groups (p=0.04). difference of 2 kg was seen between the two groups (p=0.04). Further studies are needed to verify these results . Further studies are needed to verify these results . (Simons et al, 1996).(Simons et al, 1996).

Drug therapyDrug 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

Problem and DiscussionProblem and Discussion

Q. Q. 醫師開立醫師開立 Medroxyprogestrone(500mg/tab.)1#QDMedroxyprogestrone(500mg/tab.)1#QD 是是否否合理？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

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 200

3

The authors conclude that MPA is able to stimulate increased food intake significantly and to reverse fat loss concomitantly in patients w

ith non-hormone-sensitive cancer. Cancer 1998;82:553–60.

補充資料補充資料

The Comparison of Farlutal and MegaplexThe Comparison of Farlutal and Megaplex

Megaplex FarlutalMegaplex Farlutal


The mechanism of action of progestational drugs:

1. It may stimulate appetite via neuropeptide Y in the CNS.1. It may stimulate appetite via neuropeptide Y in the CNS.

2. It may down-regulating the synthesis and release of 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 .



The Dosage The Dosage of progestational drugs:

Farlutal: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 weightbody 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.



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).


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