Phase III evaluation of four doses of megestrol acetate as therapy for patients with cancer anorexia and/or cachexia.

Loprinzi, Charles L.; Michalak, John C.; Schaid, D. J.; Mailliard, James A.; Athmann, Laureen M.; Goldberg, Richard M.; Tschetter, Loren K.; Hatfield, Alan K.; Morton, Roscoe F.

doi:10.1200/jco.1993.11.4.762

Cited by 202 publications

(79 citation statements)

References 9 publications

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“…Synthetic progestagens, MA and MPA, are currently the only approved drugs for CACS in Europe; their mechanism of action may be partly related to glucocorticoid activity and the ability to downregulate the synthesis of proinflammatory cytokines [40] and to increase food intake by neuropeptide Y release [41]. To date, Ͼ15 randomized, controlled studies in weight-losing cancer patients have demonstrated that MPA and MA significantly improve appetite, food intake, body weight, and sometimes nausea and emesis, whereas in most trials, no definite improvement in global QoL was observed [42][43][44][45][46]. The weight gain observed with progestagens consists mainly of water and fat mass [47], having virtually no influence on LBM and functional activity [48].…”

Section: Discussionmentioning

confidence: 99%

Randomized Phase III Clinical Trial of Five Different Arms of Treatment in 332 Patients with Cancer Cachexia

et al. 2010

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Purpose. A phase III, randomized study was carried out to establish the most effective and safest treatment to improve the primary endpoints of cancer cachexia-lean body mass (LBM), resting energy expenditure (REE), and fatigue-and relevant secondary endpoints: appetite, quality of life, grip strength, Glasgow Prognostic Score (GPS) and proinflammatory cytokines.Patients and Methods. Three hundred thirty-two assessable patients with cancer-related anorexia/cachexia syndrome were randomly assigned to one of five treatment arms: arm 1, medroxyprogesterone (500 mg/day) or megestrol acetate (320 mg/day); arm 2, oral supplementation with eicosapentaenoic acid; arm 3, L-carnitine (4 g/day); arm 4, thalidomide (200 mg/day); and arm 5, a combination of the above. Treatment duration was 4 months.Results. Analysis of variance showed a significant difference between treatment arms. A post hoc analysis showed the superiority of arm 5 over the others for all primary endpoints. An analysis of changes from baseline showed that LBM (by dual-energy X-ray absorptiometry and by L3 computed tomography) significantly increased in arm 5. REE decreased significantly and fatigue improved significantly in arm 5. Appetite increased significantly in arm 5; interleukin (IL)-6 decreased significantly in arm 5 and arm 4; GPS and Eastern Cooperative Oncology Group performance status (ECOG PS) score decreased significantly in arm 5, arm 4, and arm 3. Toxicity was quite negligible, and was comparable between arms. Conclusion. The most effective treatment in terms of all three primary efficacy endpoints and the secondary endpoints appetite, IL-6, GPS, and ECOG PS score was the combination regimen that included all selected agents. The Oncologist 2010;15:200 -211

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Section: Discussionmentioning

confidence: 99%

Randomized Phase III Clinical Trial of Five Different Arms of Treatment in 332 Patients with Cancer Cachexia

et al. 2010

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“…From September 1993, MEGACE was approved by the Food and Drug Administration in the United States for the treatment of anorexia, cachexia or unexplained weight loss in patients with AIDS. MEGACE has been found to improve appetite, caloric intake and nutritional status in several clinical trials [80][81][82][83][84][85][86][87][88][89][90] . Recently a meta-analysis of 35 trials, comprising 3963 patients, for the effectiveness of MEGACE was conducted [91] , demonstrating a benefit of MEGACE compared with placebo, particularly with regard increase the catabolic response, leading to unsustainable levels of fat and muscle mobilization and levels of muscle depletion that cause significant morbidity and mortality.…”

Section: Megacementioning

confidence: 99%

Cancer cachexia, mechanism and treatment

Aoyagi¹,

Terracina²,

Ali³

et al. 2015

WJGO

352

282

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It is estimated that half of all patients with cancer eventually develop a syndrome of cachexia, with anorexia and a progressive loss of adipose tissue and skeletal muscle mass. Cancer cachexia is characterized by systemic inflammation, negative protein and energy balance, and an involuntary loss of lean body mass. It is an insidious syndrome that not only has a dramatic impact on patient quality of life, but also is associated with poor responses to chemotherapy and decreased survival. Cachexia is still largely an underestimated and untreated condition, despite the fact that multiple mechanisms are reported to be involved in its development, with a number of cytokines postulated to play a role in the etiology of the persistent catabolic state. Existing therapies for cachexia, including orexigenic appetite stimulants, focus on palliation of symptoms and reduction of the distress of patients and families rather than prolongation of life. Recent therapies for the cachectic syndrome involve a multidisciplinary approach. Combination therapy with diet modification and/or exercise has been added to novel pharmaceutical agents, such as Megestrol acetate, medroxyprogesterone, ghrelin, omega-3-fatty acid among others. These agents are reported to have improved survival rates as well as quality of life. In this review, we will discuss the emerging understanding of the mechanisms of cancer cachexia, the current treatment options including multidisciplinary combination therapies, as well an update on new and ongoing clinical trials.

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“…However, only 8 -15% of patients experienced weight gain of Ն10% over baseline. 10 Unfortunately, the weight gained primarily is fluid and fat (not muscle mass) and when added to standard chemotherapy for small cell lung carcinoma does not result in improvement in terms of response, survival, or quality of life. 11,12 In addition, adrenal suppression has been reported with this agent.…”

Section: Discussionmentioning

confidence: 99%