Eficácia e segurança do acetato de megestrol para o tratamento da anorexia nos cuidados paliativos: revisão rápida de evidências / Efficacy of the megestrol acetate in the treatment of anorexia in palliative care: a rapid response review of evidence

Acetato de Megestrol (AM). Indicação: Tratamento da Síndrome anorexia-caquexia (SAC) em doentes crônicos em fase de cuidados paliativos. Objetivo: Avaliar a eficácia e segurança do uso do AM em doentes crônicos sob cuidados paliativos. Métodos: Foi realizada uma revisão rápida de revisões sistemáticas, com levantamento bibliográfico nas bases de dados PUBMED, EMBASE, SCOPUS, BVS, Cochrane Library, Web Of Science e em registros de revisões sistemáticas e ensaios clínicos. A qualidade metodológica dos estudos incluídos foi avaliada com a ferramenta AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews Version 2). Resultados: A busca recuperou um total de 2.370 após exclusão das duplicatas; 1003 estudos foram triados pelo título e resumo, de acordo com os critérios de inclusão previamente estabelecidos. Dezesseis RSs foram selecionadas para leitura completa, sendo que, destas, apenas 1 RS foi classificado com alta qualidade metodológica. Após a análise dos ECR das RSs excluídas, um ECR foi incluído considerando os critérios de inclusão. Dois estudos adicionais publicados posteriormente a RS de Ruiz-Garcia et al. Conclusão: Com base nas evidências disponíveis, o AM proporciona leve ganho de peso e melhora o apetite, porém esses resultados não refletem melhoria na qualidade de vida dos pacientes, além de haver risco considerável de desenvolver fenômenos tromboembólicos

Megestrol acetate (MA). Indication: treatment of anorexia-cachexia syndrome (ACS) in chronic diseases patients, under palliative care. Objective: Evaluate the efficacy and safety of the use of Megestrol Acetate to treat ACS in patients under palliative care. Methods: Rapid review protocol of Systematic Reviews and Clinical Trials. A literature Search was performed in PUBMED, EMBASE, SCOPUS, BVS, Cochrane Library, Web of Science databases and in clinical trials records, following a predefined strategy. The methodological quality of the selected articles was assessed through AMSTAR-2 (Assessing the Methodological Quality of Systematic Reviews Version 2) tool. Results: the search resulted in 2,370 articles, after the duplicates exclusion. 1003 were analyzed by tittle and abstracts according the inclusion criteria. 16 were selected for full text reading, and only one considered to have high methodological quality. After the analyses of the Randomized Clinical Trials of the excluded Systematic Reviews, one RCT was included. Two additional studies published after the SR of Ruiz-Garcia et al were also included. Conclusion: based on available evidence, the MA promoted a small gain in body weight and a slight appetite improvement, although these results did not imply an enhancement in their quality of life. Moreover, there is a considerable risk of causing thromboembolic disorders

Conservative therapy with metformin plus megestrol acetate for endometrial atypical hyperplasia / 부인종양

OBJECTIVE: To compare the efficacy of metformin plus megestrol acetate (MA) with that of MA alone for treating endometrial atypical hyperplasia (EAH). METHODS: This pilot study included 16 EAH patients who met at least one metabolic syndrome (MS) criterion and received either adjunctive metformin plus MA (MET group) or MA monotherapy (MA group). Each patient in the MA group received 160 mg of MA daily, whereas patients in the MET group received the same dose of MA plus 0.5 g of metformin thrice daily. Treatment response was assessed by histological examination of dilation and curettage specimens obtained after 12 weeks of therapy. RESULTS: Each group had eight patients, and half of the patients in each group were diagnosed with MS. The complete response (CR) rate was 75% (6/8) in the MET group and 25% (2/8) in the MA group (p=0.105). Complications of MS did not affect the response rates in either group. In the MET group, 75% (3/4) of the patients had CR in the presence or absence of MS. In the MA group, 50% (2/4) of the patients with MS had CR, whereas no patient without MS had CR. No irreversible toxicities were observed. CONCLUSION: Metformin plus MA may be a potential alternative therapy for treating EAH, and the MS status of patients may have no effect on the efficacy of metformin plus MA therapy.

Safety of Megestrol Acetate in Palliating Anorexia-Cachexia Syndrome in Patients with Castration-Resistant Prostate Cancer

There are concerns whether megestrol acetate (MA) stimulates the growth of prostate cancer in castration-resistant prostate cancer (CRPC). We evaluated the effect of cumulative doses of MA on the disease-specific survival (DSS) in patients with CRPC who were receiving Docetaxel-based chemotherapy. From July 2003 through June 2009, we identified 109 consecutive patients with CRPC and who had received docetaxel-based chemotherapy. Of these patients, 68 (62.4%) have not received MA, whereas 21 patients (19.3%) and 20 patients (18.3%) had received low dose MA (total 18,400 mg), respectively. We assessed the effect of several variables on DSS. None of the clinicopathological variables differed among the three groups. When comparing DSS using Kaplan-Meier analysis, there was no statistically significant survival differences among the three groups (P = 0.546). Using multivariate Cox proportional analyses with backward elimination, the number of docetaxel cycles was only significant factor predicting DSS (HR: 0.578, 95% CI: 0.318-0.923, P = 0.016). Cumulative doses of MA as adjuvant treatment for patients with CRPC and who are receiving docetaxel-based chemotherapy, did not affect their DSS. Therefore, MA can be safely administered in cachexic patients with CRPC.

Neo-adjuvant chemotherapy of megestrol acetate in bereast cancer: short-term clinical study / 国际外科学杂志

Objective To observe the role of short-term use of megestrol acetate in reducing the toxicity of chemotherapy in breast cancer and in improving the quality of life of patients, as well as its impact on neo-adjuvant chemotherapy effects. Methods The effection of adjuvant chemotherapy, toxicity, and the quality of life of 158 patients with breast cancer were investigated by a retrospective control study. The data were statistically analysized by X~2 test. Results There was no significant difference of neo-adjuvant chemotherapy effects between Megestrol acetate + CEF chemotherapy group and vitamin C + CEF chemotherapy group (Megestrol acetate + CEF chemotherapy group was 74. 84%, vitamin C + CEF chemotherapy group was 76.15) ; Megestrol acetate + CEF chemotherapy group had more modest bone marrow suppression and gas-trointestinal reactions and better food intake, weight, KPS score than vitamin C + CEF Chemotherapy group, all the differences being statistically significant (P < 0.05). Conclusion Short-term use of megestrol ace-tate can reduce the adverse effects derived from chemotherapy of breast cancer and improve the quality of life of patients with breast cancer and had no effects on the efficacy of the neo-adjuvant chemotherapy.

Secondary Adrenal Insufficiency Associated with Megestrol Acetate in a Patient with Lung Cancer / 결핵및호흡기질환

Loss of appetite is an important factor in the quality of life for advanced cancer patients. Megestrol acetate is used to stimulate appetite, but it can cause suppression of the pituitary adrenal axis due to the affinity of the glucocorticoid receptor. Adrenal insufficiency is a life threatening disorder if left, untreated, but the initial clinical symptoms of the patients are vague. Awareness of the glucocorticoid-like activity of megestrol acetate and its side effects are important for the diagnosis of adrenal insufficiency. We present a case of secondary adrenal insufficiency associated with megestrol acetate in a patient with lung cancer.

Low Dose Megestrol Acetate for Maintenance Hemodialysis Patients / 대한신장학회지

PURPOSE: Maintenance hemodialysis (HD) patients have a high prevalence of malnutrition and inflammation. Megestrol acetate (MA) has been shown to increase appetite in cancer patients but the usual dose of MA (400-800 mg/day) was associated with serious side effects in HD patients. We evaluated the changes in nutritional and inflammatory parameters after low dose of MA treatment in malnourished HD patients METHODS: Inclusion criteria were maintenance HD patients who showed serum albumin <3.5 g/dL or <4.0 g/dL with anorexia. Serum chemical parameters, cytokines, Subjective Global Assessment, dry weight, Kt/V, nPCR, SF36 quality of life, fat free mass (FFM), and body fat mass (BFM) were measured. Patients were instructed to take 5 mL (200 mg) of MA solution once a day. RESULTS: Fourteen patients (seven male, age 52+/-10 years, mean HD duration 48+/-59 months) were included. One patient died of pneumonia. Seven patients dropped out because they refused to take the drug after one to three months of treatment; two of them complained of thirst, three of them ate too much, and two had both. Six patients (four male and two female) have completed six months of study. Serum albumin (3.1+/-0.5 to 3.6+/-0.4 g/dL), TIBC (184.2+/-27.9 to 205.0+/-25.8 microgram/ dL), BFM (11.9+/-5.7 to 16.6+/-7.4 kg), protein intake (57.0+/-32.5 to 68.7+/-39.2 g/day), and energy intake (1,521+/-690 to 1,724+/-879) were increased. Serum CRP and IL-6 decreased without statistical significance. No significant adverse effects were observed in all patients who had completed study. CONCLUSION: Low dose MA can improve the nutritional status, inflammation, and anorexia in maintenance HD patients.

Thrombosis in Patients with Acquired Immunodeficiency Syndrome

Patients with HIV infection may be at increased risk of thrombosis. A variety of mechanism have been proposed to account for hypercoagulability in HIV-infected patients. These include decreased plasma concentrations of protein S, opportunistic infection, tumor such as Kaposi's sarcoma, drugs such as megestrol acetate, protease inhibitor, and presence of anticardiolipin antibody. The authors report three cases of thrombosis in AIDS patients. One case was renal vein thrombosis associated with abnormalities of protein S and anticardiolipin IgG. Two cases were pulmonary embolism associated with megestrol acetate.

Thrombosis in Patients with Acquired Immunodeficiency Syndrome

Patients with HIV infection may be at increased risk of thrombosis. A variety of mechanism have been proposed to account for hypercoagulability in HIV-infected patients. These include decreased plasma concentrations of protein S, opportunistic infection, tumor such as Kaposi's sarcoma, drugs such as megestrol acetate, protease inhibitor, and presence of anticardiolipin antibody. The authors report three cases of thrombosis in AIDS patients. One case was renal vein thrombosis associated with abnormalities of protein S and anticardiolipin IgG. Two cases were pulmonary embolism associated with megestrol acetate.

Determination of Main Component in Megestrol Acetate Tablets by RP-HPLC / 中国药房

OBJECTIVE:To establish the RP-HPLC method for the determination of main component in megestrol acetate tablets.METHODS:RP-HPLC was carried out using a SinoChrom OPS-AP column with column temperature kept at room temperature.The detection wavelength was set at 288 nm.The mobile phase was composed of water-acetonitrile(20∶80,containing 2% triethylamine,pH 5.28)at a flow rate of 1.0 mL?min-1 with dixiben served as internal standard.The injection volume was 20 ?L.RESULTS:The standard curve was linear over the range of 7～336 ?g?mL-1 for megestrol acetate(r=0.999 6)and its recovery rate was 99.95%(RSD=0.51%).CONCLUSION:The method is simple,reproducible and accurate,and it is applicable for the determination of the megestrol acetate tablets.

A successful twin pregnancy after conservative therapy of endometrial cancer / 대한산부인과학회지

Endometrial cancer is increasing in South Korea. In young women, endometrial cancer can be treated by progestins for preserving fertility. We experienced a successful case of twin pregnancy after conservative therapy of endometrial cancer with Megestrol acetate. Ovulation induction and intrauterine insemination was done. A brief review of related literature was done.

Megestrol acetate combined with chemotherapeutic drugs improved the quality of life in cancer patients / 中国基层医药

Objective To survey the effect of high dose MA combined with chemotherapeutic drugs on the quality of life(QOL) in cancer patients.Methods 61 patients were divided into two groups:the control group were treated with chemotherapeutic,the test group were given high-dose MA in addition.Results The patients accepting MA had better appetite,gained body weight,and vomited less.Conclusion High-dose MA can improve the QOL in cancer patients.

A case of treatment using high-dose Megestrol Acetate (Megace(R)) combined with PDT (Photodynamic Therapy) on early stage of endometrial carcinoma, in nulliparous woman / 대한산부인과학회지

Endometrial carcinoma is predominantly a disease of postmenopausal women, so we don't have to consider fertility. But in case of young women who want to preserve their fertility, it is very difficult to approach. We experienced one case of treatment using high-dose Megestrol Acetate (Megace(R)) combined with PDT (Photodynamic Therapy) on early stage of endometrial carcinoma, in young aged woman who wanted to preserve her fertility. And, we described briefly clinicopathologic findings, reviews of literatures and possibility of combined therapy with Megestrol and PDT.

Treatment Efficacy of High-Dose Megestrol Acetate (Megace) in Young Women with Early Stage of Endometrial Carcinoma / 대한부인종양콜포스코피학회잡지

The effectiveness of progestogens in advanced and recurrent endometrial carcinoma has been widely accepted. But the use of progestogens in young women with early stage of endometrial carcinoma (Stage Ia) is controversial. Some authors reported that progestogens alone therapy improved or cured the endometrial pathology in young patients with early stage of endometrial carcinoma. The response to the progestogens has known to be better in cases of early stage, well-differentiated histologic type and narrow depth of invasion. We used the high-dose megestrol acetate (Megace(R)) as the primary treatment in four young women with early stage of endometrial carcinoma (Stage Ia) for the purpose of saving the fertility. We made the patients to have 320~400 mg of Megace(R) per day for 3 months, and then repeated the endometrial curettage for the purpose of finding changes of endometrial pathology. Three cases revealed no response to the Megace(R), so they were operated later. One case showed the resolution of endometrial pathology and delivered a baby following therapy. There have been no evidences of clinical recurrence in all cases. Even though the therapeutic efficacy is limited, high-dose therapy with megestrol acetate can be used as primary therapy in young women with early stage of endometrial carcinoma.

Additional megestrol acetate with cis-platinum combination regimens in treatment of advanced ovaian epithelial cancer.

Patients with advanced ovarian epithelial cancer were randomized for additional oral megestrol acetate 160 mg/day for 3 weeks and repeated simultaneously every cycle of the three cis-platinum combination regimens. Fifteen patients of AP and 18 cases of AP plus megestrol acetate showed a higher incidence of weight gain 26.66% versus 94.44% (P<0.05), lower incidence of nausea-vomiting 73.33% versus 22.22% (P<0.05), increase of appetite and sense of well being 26.66% versus 77.77% (P<0.05), and incidence of good performance 53.33% versus 66.66% (P>0.05). Fifteen cases of EP and 17 cases of EP plus megestrol acetate achieved a higher incidence of weight gain 20.00% versus 88.23% (P<0.05), incidence of nausea-vomiting 73.33% versus 41.17% (P>0.05), better incidence of good appetite and sense of well being 20.00% versus 70.58% (P<0.05), and incidence of good performance 26.66% versus 64.70% (P>0.05). Nineteen cases of CAP and 15 cases of CAP plus megestrol acetate achieved a higher incidence of weight gain 31.57% versus 86.66% (P<0.05), lower incidence of nausea-vomiting 89.47% versus 40.00% (P>0.05), incidence of good appetite and sense of well being 47.36% versus 80.00% (P>0.05), and incidence of good performance 57.89% versus 66.66% (P>0.05). The response rate of disease to the additional megestrol acetate of the three regimens showed no significant change.