Transcript High-dose progestins for the treatment of cancer anorexia

High-dose progestins for the
treatment of cancer anorexia
- cachexia syndrome
主講人:徐嫈惠
2008/01/29
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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-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).
Pathogenetic mechanisms of anorexia-cachexia
Pathogenetic mechanisms of anorexia-cachexia
Medroxyprogesterone acetate
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簡介
Medroxyprogesterone acetate(MPA)是由黃體激素
(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
有Methyl group與17位置有acetoxy group。
Medroxyprogesterone acetate
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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
2.停經後婦女之乳癌
3.攝護腺癌
4.伴有惡病質(cachexia)之末期癌症
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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。
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。
晚期和轉移性子宮內膜癌: 500 mg/day
晚期和轉移性攝護腺癌: 500 mg/day。
Non-FDA Labeled Indications
Loss of appitite
a) Overview: FDA Approval: Adult, no; Pediatric, no
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).
Drug therapy
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Progestagens ( medroxyprogesterone acetate) are the first-line
therapy for cancer anorexia.
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Medroxyprogesterone has been shown to increase appetite and
food intake with stabilization of body weight at a dose of 1000 mg
(500 mg twice).
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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 Discussion
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Q. 醫師開立Medroxyprogestrone(500mg/tab.)1#QD是否
合理？
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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
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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
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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.
補充資料
The Comparison of Farlutal and Megaplex
Megaplex
Farlutal
The Comparison of Farlutal and Megaplex
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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 .
CA Cancer J Clin 2002;52:72-91
The Comparison of Farlutal and Megaplex
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The Dosage of progestational drugs:
Farlutal:
1. Dosage: range from 500 mg/day to 4000 mg/day.
2. 1000 mg/day was reported improvement of appetite and
body weight .
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
The Comparison of Farlutal and Megaplex
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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