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

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Text of High-dose progestins for the treatment of cancer anorexia - cachexia syndrome 主講人 : 徐嫈惠...

  • High-dose progestins for the treatment of cancer anorexia - cachexia syndrome:2008/01/29

  • 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-cachexiaSeveral 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).

  • Pathogenetic mechanisms of anorexia-cachexia

  • Pathogenetic mechanisms of anorexia-cachexia

  • Medroxyprogesterone acetate Medroxyprogesterone acetate(MPA) (17-OH-progesterone) -6 Methyl group17acetoxy group

  • Medroxyprogesterone acetate 1. 2. 3. 4.(cachexia) 1.1000mg2 2.100~1000 mg2~3 : 1000 mg/day : 500 mg/day : 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 therapyProgestagens ( 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 DiscussionQ. Medroxyprogestrone(500mg/tab.)1#QD

    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

  • ConclusionCancer 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;82:55360.

  • The Comparison of Farlutal and Megaplex Megaplex Farlutal

  • 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 .

    CA Cancer J Clin 2002;52:72-91

  • The Comparison of Farlutal and MegaplexThe 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 MegaplexThe 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