VA Class:AN500
Megestrol acetate, a synthetic progestin, is an antineoplastic agent and appetite stimulant.
Megestrol acetate is used in the palliative management of recurrent, inoperable, or metastatic endometrial carcinoma or breast cancer. The drug is also used as an adjunct to surgery or radiation. Megestrol acetate does not replace appropriate methods of treatment of advanced endometrial carcinoma or breast cancer such as surgery or radiation. The drug currently is not recommended for use in other neoplastic diseases, but studies are under way. Beneficial response to therapy has been reported in approximately one-half of patients with recurrent or metastatic adenocarcinoma of the endometrium receiving an adequate course of treatment with megestrol acetate. Objective response as evidenced by a decrease in the size of a soft tissue mass, radiographic evidence of improvement in metastatic lesions, cessation of vaginal bleeding, or decrease in size of fungating vaginal lesions were maintained for a minimum of six months in 27% of he patients studied. Precise evaluation of megestrol acetate effectiveness is difficult, however, because of potential variables and the impracticality of including “control patients” in such studies.
Megestrol acetate is used in the management of anorexia, cachexia, or an unexplained, substantial weight loss (i.e., loss of 10% or more of baseline body weight) in patients with acquired immunodeficiency syndrome (AIDS)102, 104, 106, 107, 108, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136 and has been designated an orphan drug by the US Food and Drug Administration (FDA) for this use.106 In a multicenter, randomized, double-blind, placebo-controlled study in patients with AIDS, cachexia and/or anorexia, and substantial weight loss, therapy with megestrol acetate 100, 400, or 800 mg daily for 12 weeks resulted in a weight gain of about 0.8, 1.9, or 3.5 kg, respectively, compared with an average weight loss of about 0.7 kg in those receiving placebo.121 In addition, a weight gain of 2.3 kg or more occurred in about 64 or 57% of patients receiving 800 or 400 mg of megestrol acetate daily, respectively, compared with 24% of those receiving placebo.121 Weight gain was associated with increases in nonwater body weight; edema developed or worsened in only 3 patients.121 Increased appetite occurred in about 89, 68, or 72% of patients receiving 800, 400, or 100 mg of megestrol acetate daily, respectively, compared with 50% of those receiving placebo at the last evaluation of the 12-week study; however, a subjective improvement in weight, appetite, appearance, and an overall sense of well-being and increased caloric intake during megestrol therapy was favorably reported only in those receiving 800 mg of megestrol acetate daily compared with those receiving placebo.121 In another multicenter, randomized, double-blind, placebo-controlled study in patients with AIDS, anorexia and/or cachexia, and substantial weight loss, therapy with 800 mg daily of megestrol acetate resulted in an average weight gain of about 5 kg compared with an average weight loss of about 1 kg in those receiving placebo.121 Weight gain was associated with increases in nonwater body weight; edema was not reported in any of the patients receiving megestrol therapy.121 Increased appetite occurred in about 67% of patients receiving megestrol compared with 38% of those receiving placebo;121 however, daily caloric intake was similar in patients receiving megestrol and those receiving placebo.121
Results of other controlled122, 123, 126, 128, 130 and uncontrolled102, 104, 105, 115, 125, 132 studies also indicate that megestrol therapy (100-800 mg daily for 2-72 weeks) is associated with weight gain (about 3-7 kg), increased appetite, and an overall sense of well-being in patients with HIV infection and severe anorexia and/or cachexia; no improvement in immunologic function has been observed to date,130 although some increases (mean increases of 69/ mm3) in helper/inducer (CD4+) T-cell counts have been reported occasionally.122 Several treatment failures, however, have been reported in patients receiving up to 640 mg/day of megestrol for the management of anorexia and cachexia associated with HIV infection.104, 105, 115
Megestrol acetate also has been used to stimulate appetite and promote weight gain in a limited number of patients with cachexia associated with neoplastic disease†.100, 101, 103, 108, 116, 117, 118, 119, 134, 135 In a large controlled study in patients with anorexia (i.e., an estimated daily caloric intake of less than 20 calories/kg) and/or cachexia (i.e., a weight loss of at least 2.3 kg in the period up to 2 months preceding the study) associated with advanced cancer (excluding endometrial carcinoma and breast cancer)†, therapy with megestrol acetate (800 mg daily) for a median time of 1.6 months resulted in a weight gain of at least 6.8 kg in 16% of patients compared with 2% of those receiving placebo; in megestrol-treated patients, this weight gain was 10% or more of baseline body weight.116, 119 Patients receiving megestrol acetate reportedly had a higher incidence of improved appetite and food intake and a lower incidence of nausea and vomiting than those receiving placebo.116, 119 Some evidence suggests that weight gain occurs in approximately one third of patients with metastatic carcinoma receiving usual dosages of megestrol acetate (160 mg daily) for the treatment of anorexia.100, 103, 115 However, increased appetite and weight gain (median weight gain of 5.1 kg; range: 0.9-20.1 kg) occurred in nearly all patients who received 6 weeks or more of high-dose (480-1600 mg daily) megestrol therapy for the palliative management of advanced breast cancer.101 Current evidence suggests that the rate of weight gain in patients with neoplastic disease is not related to antineoplastic response, pretreatment body weight, or extent of disease;100, 101, 115 however, some,100, 103, 108, 110, 116 but not all,117 evidence indicates that megestrol-induced weight gain may be dose-related.100, 103, 108, 110, 116
Megestrol therapy generally has been well tolerated by most patients receiving the drug for the management of cachexia,100, 101, 102, 103, 116 and many patients with HIV infection or neoplastic disease have reported a subjective improvement in their sense of well-being during megestrol therapy.100, 101, 102, 103, 110, 121 However, hyperpnea reportedly has occurred in at least 2 HIV-infected patients receiving 240 mg of the drug daily.107 (See Cautions.)Additional studies are necessary to fully establish the safety and efficacy of megestrol for the management of cachexia associated with HIV infection or neoplastic disease,100, 102, 103, 104, 108, 116, 119 and to determine the optimum dosage of megestrol for these conditions.100, 105, 116, 119 In addition, some clinicians have mentioned theoretically 104, 105 the possible effects of megestrol's potential glucocorticoid action on HIV and the expression of HIV infection.104, 112
Megestrol acetate has been used alone or in combination or sequential regimens with estrogens for ovulation control in the prevention of conception†. The drug has also been used in the treatment of prostatic hypertrophy†, endometriosis†, and endometrial hyperplasia†.
Megestrol acetate is administered orally.
Megestrol acetate oral suspensions containing 200 mg/5 mL are not bioequivalent with the more concentrated oral suspension containing 625 mg/5 mL (Megace® ES).138 Threfore, the formulations are not interchangeable on a mg-per-mg basis.138 Patients receiving Megace® ES should be informed about the formulation differences to avoid overdosing or underdosing of the drug.138
The usual dosage of megestrol acetate in the palliative treatment of advanced breast cancer has been 160 mg daily in 4 equally divided doses, although some clinicians suggest that single daily doses may be justified based on the drug's pharmacokinetics.115 However, higher dosages (480-1600 mg daily in divided doses) are being evaluated, and the optimum dosage remains to be established.100, 108, 110, 114
Dosages substantially higher than usual currently are being investigated for this and other cancers.
The usual dosage of megestrol acetate in the palliative treatment of advanced endometrial carcinoma is 40-320 mg daily administered in divided doses. An adequate trial period for determining the antineoplastic effectiveness of megestrol acetate is 2 months.
Dosages substantially higher than usual currently are being investigated for this and other cancers.
The initial dosage of megestrol acetate in the management of anorexia, cachexia, or an unexplained, substantial weight loss in adults with acquired immunodeficiency syndrome (AIDS) is 800 mg daily.121, 122, 126, 127, 128, 130 Lower dosages (e.g., 100-400 mg daily) of megestrol acetate also have been used effectively in the management of AIDS-related cachexia.102, 121, 125, 126, 127, 129, 130, 132
Alternatively, when the more concentrated (625 mg/5 mL) formulation of megestrol acetate oral suspension is used (Megace® ES) in the management of anorexia, cachexia, or an unexplained, substantial weight loss in adults with AIDS, the usual initial dosage is 625 mg daily.138 Based on clinical experience with the original less concentrated formulation (200 mg/5 mL), clinically effective dosages of the more concentrated formulation (625 mg/5 mL) are expected to range from 312.5-625 mg daily.138
For the management of anorexia or cachexia in adults with neoplastic disease†, megestrol acetate dosages of 480-600 mg daily generally have been used. However, some patients may exhibit weight gain with dosages as low as 160 mg daily.
Megestrol acetate usually is well tolerated. The manufacturer states that no statistically significant differences regarding laboratory abnormalities; new opportunistic infections; lymphocyte, helper/inducer (CD4+, T4+) T-cell, and suppressor/cytotoxic (CD8+, T8+) T-cell counts; or skin reactivity have been observed in patients with AIDS-related cachexia who were receiving 100, 400, or 800 mg of megestrol acetate daily for 12 weeks.121 The manufacturer states that no serious adverse effects have occurred in studies in which megestrol acetate was administered in dosages as high as 800 mg daily.
Adverse GI effects of megestrol occurring in at least 5% of patients include diarrhea,110, 121 flatulence,121 nausea,120, 121 and vomiting.120, 121 Constipation, dyspepsia,121 dry mouth, increased salivation, and oral candidiasis have been reported in about 1-4% of patients.110
Impotence and decreased libido have been reported in at least 5% of patients with AIDS-related cachexia receiving megestrol.121 Urinary frequency,110, 121 urinary incontinence,121 and urinary tract infection121 also have been reported. Vaginal bleeding and discharge (including breakthrough bleeding) have occurred in patients receiving usual dosages of the drug for the palliative management of breast cancer.108
Hypertension121 or mild elevation in blood pressure (approximately 10 mm Hg)110 has been reported in patients receiving high-dose (480-1600 mg daily) megestrol acetate therapy. Cardiomyopathy,121 palpitation,121 chest pain,121 chest pressure,110 edema,120, 121 peripheral edema,121 and congestive heart failure also have been reported.110 These adverse effects generally were mild in severity, and manifestations such as elevated blood pressure and congestive heart failure reportedly resolved following initiation of diuretic therapy or adjustment of the patient's preexisting antihypertensive regimen.110
Pneumonia has been reported in about 2% of patients receiving megestrol acetate for AIDS-related cachexia.121 Dyspnea,110, 120, 121 cough,121 pharyngitis,121 and lung disorder occurred in about 1-3% of patients receiving megestrol.121
Hyperpnea has been reported in at least 2 HIV-infected patients receiving 240 mg of megestrol acetate daily for the management of cachexia.107 Although the mechanism for this adverse effect has not been clearly established, it was suggested that megestrol, like other progestins, may stimulate respiration, particularly in patients receiving relatively high dosages of the drug.107
Insomnia, headache, asthenia, paresthesia, confusion, seizures, depression, neuropathy, hypesthesia, and abnormal thinking have been reported in patients with AIDS-related cachexia receiving megestrol acetate.121
Fever, anemia, leukopenia, hepatomegaly, pain (including abdominal pain), infections, candidiasis, herpes, pruritus, vesiculobullous rash, sweating, skin disorders, amblyopia, increases in LDH, and sarcoma have been reported in patients with AIDS-related cachexia receiving megestrol acetate therapy.121 Carpal tunnel syndrome, thromboembolic phenomena (e.g., deep-vein thrombophlebitis, pulmonary embolism), gynecomastia, tumor flare (with or without hypercalcemia), hyperglycemia, rash, feeling of coldness, and alopecia also have been reported in patients receiving megestrol therapy.2, 120, 121, 132 In at least one patient receiving megestrol therapy for AIDS-related cachexia, diabetes mellitus (requiring insulin therapy) was reported.136
Weight gain100, 101, 102, 103, 108, 110, 114, 116, 117, 118, 119, 120, 121 and increased appetite100, 101, 102, 103, 108, 110, 114, 116, 117, 118, 119, 120, 121 have been reported in some patients receiving usual or higher dosages of megestrol acetate, and some evidence suggests that such effects may be dose-related; these effects generally are considered therapeutic rather than adverse effects in patients with anorexia and cachexia associated with neoplastic disease or HIV infection.100, 101, 102, 103, 108, 110, 114, 116, 117, 118, 119, 121 (See Pharmacology and also see Uses: Cachexia.)
Precautions and Contraindications
Megestrol acetate therapy for weight loss should be initiated only after treatable causes (e.g., possible malignancies; systemic infections; GI disorders [which may affect absorption]; endocrine, renal, or psychiatric diseases) of the condition have been evaluated.121 Although the potential glucocorticoid effects of megestrol acetate have not been evaluated in patients with HIV infection, laboratory evidence of megestrol-induced adrenal suppression has been observed; however, it appears to be clinically insignificant.121 Effects of megestrol acetate on viral replication have not been determined.121
Patients should be advised that megestrol acetate should only be used as directed by a clinician, and patients should be advised to report any adverse effects that occur during megestrol acetate therapy to their clinician.121 Although megestrol acetate has been used extensively in the management of endometrial carcinoma and breast cancer, experience with the drug in women with HIV infection is limited.121 In one clinical study using megestrol acetate in women with HIV infection, breakthrough bleeding occurred in all patients receiving the drug.121
Megestrol acetate is not intended for prophylactic use to avoid weight loss.121 Megestrol acetate should not be used as a diagnostic test for pregnancy.120, 121
Safety and efficacy of megestrol acetate in children have not been established.121
Mutagenicity and Carcinogenicity
Mutagenicity studies of megestrol acetate have not been performed to date.121
In female beagles receiving megestrol acetate dosages of 0.01, 0.1, or 0.25 mg/kg daily for 7 years, both benign and malignant breast tumors occurred.121 No tumors were reported in female monkeys receiving megestrol acetate dosages of 0.01, 0.1, or 0.5 mg/kg daily for 10 years.121 Pituitary tumors were observed in female rats receiving megestrol acetate dosages of 3.9 or 10 mg/kg daily for 2 years.121 The relevance of these animal findings to humans has not been established; however, the drug should be used only when the potential benefits justify the possible risks to the patient.121 It also should be considered that megestrol acetate dosages in these animal studies were 1.3-53.2 times lower than the usual recommended (13.3 mg/kg daily) dosage in humans.121
Pregnancy, Fertility, and Lactation
Although there are no adequate and controlled studies to date using megestrol acetate in pregnant women, the drug has been shown to produce fetal harm in rats.121 Administration of the drug to rats produced decreases in fetal weight and live births and feminization of male fetuses.121 No teratogenicity studies in animals have been performed using megestrol acetate dosages that are clinically relevant to humans.121 Although progestins have been used beginning in the first trimester of pregnancy to prevent habitual abortion, there is no adequate evidence from well-controlled studies to substantiate the efficacy of progestins for these uses during any phase of pregnancy; however, there is evidence of potential adverse effects on the fetus when these drugs are administered during pregnancy. In addition, in most women, the cause of abortion is a defective ovum, which progestins could not be expected to influence. Because of their uterine-relaxant effects, progestins may delay spontaneous abortion of fertilized defective ova. There is evidence of increased risk of hypospadias in male neonates associated with progestin use during pregnancy; however, there are insufficient data about the risk in female fetuses. Because of increased genital abnormalities caused by progestins in both male and female fetuses, the manufacturer states that megestrol acetate is not recommended during pregnancy. If a woman becomes pregnant while receiving megestrol acetate or is inadvertently exposed to the drug during pregnancy, she should notify her physician and should be advised of the potential risks to the fetus. Women of childbearing potential should be advised not to become pregnant while receiving megestrol acetate therapy, and they should be advised to use an effective form of contraception while receiving the drug.121
Reproduction studies in female rats using megestrol acetate dosages of 0.05-12.5 mg/kg daily (lower than the recommended [13.3 mg/kg daily] dosage in humans) have revealed evidence of impaired fertility in male offspring of mothers receiving megestrol acetate; similar results were obtained in dogs.121 No information on fertility (spermatogenesis) in male animals receiving megestrol acetate is currently available.121
The manufacturer states that because of the potential for serious adverse reactions to megestrol acetate in nursing infants, women receiving the drug should discontinue nursing.121
No serious unexpected adverse effects were reported in patients with AIDS-related cachexia121 or with breast cancer110 receiving megestrol acetate dosages up to 1200 or 1600 mg daily,121 respectively. It is not known if megestrol acetate is removed by dialysis; however, the manufacturer states that because of the low solubility of the drug, megestrol acetate probably is not removed by this procedure.121
Megestrol acetate shares the actions of the progestins: induction of secretory changes in the endometrium, increase in basal body temperature, pituitary inhibition, and production of withdrawal bleeding in the presence of estrogen. In animals, the drug suppresses ovulation and produces antigonadotrophic, antiuterotrophic and antiandrogenic/antimyotrophic effects. It has slight glucocorticoid activity and a very slight degree of mineralocorticoid activity. Megestrol acetate has no estrogenic, androgenic, or anabolic activity.
The exact mechanism of the antineoplastic action of megestrol acetate has not been determined. It has been suggested that the antineoplastic effect may result from suppression of luteinizing hormone by inhibition of pituitary function. Results of one study suggested that megestrol acetate produced a local effect on the cancerous cell by converting the actively growing stroma into decidua.
The precise mechanism for megestrol-induced weight gain has not been clearly established;100, 101, 103, 108, 109, 116, 121 however, evidence from clinical studies indicates that the increase in body weight observed during megestrol therapy is related to the drug's appetite-stimulant or metabolic effects rather than its glucocorticoid-like effects or the production of edema.100, 101, 102, 103, 108, 110, 115, 116 It has been suggested that megestrol and/or its metabolites may, either directly or indirectly, stimulate appetite resulting in weight gain or may alter metabolic pathways via interference with the production or action of mediators such as cachectin (a hormone that inhibits adipocyte lipogenic enzymes).100, 101, 103, 109, 110, 111
Megestrol acetate appears to be well absorbed from the GI tract. The relative oral bioavailability of megestrol acetate suspensions and tablets has not been evaluated.121 Plasma megestrol acetate concentrations achieved with a 625-mg dose of the more concentrated oral suspension (Megace® ES 625 mg/5 mL) are equivalent to those achieved with an 800-mg dose of the original formulation (200 mg/5 mL) under fed conditions.138 Peak concentrations and AUC were 54.8 and 43.3% higher, respectively, under fed conditions compared with fasting for the concentrated suspension and were 12.9 and 24.4% higher, respectively, under fed conditions compared with fasting for the original formulation.138
Following oral administration of radiolabeled megestrol acetate, peak plasma concentrations of the drug and its metabolites were attained within 1-5 hours. Following daily oral administration of single 800-mg doses of megestrol acetate (as the suspension) for 21 days in cachectic patients with acquired immunodeficiency syndrome (AIDS) who had substantial weight loss (i.e., loss of more than 10% of baseline body weight), steady-state peak plasma megestrol concentrations on day 21 occurred about 5 hours after administration of the drug and averaged 753 ng/mL.121 Following daily oral administration of single 750-mg doses of megestrol acetate (as the suspension) in patients with asymptomatic human immunodeficiency virus (HIV; formerly HTLV-III/LAV) infection for 14 days, peak plasma megestrol concentrations occurred within 3 hours after administration of the drug and averaged about 490 ng/mL.121 Megestrol acetate appears to be completely metabolized in the liver to free steroids and glucuronide conjugates of 17α-acetoxy-2α-hydroxy-6-methylpregna-4,6-diene-3,20-dione, 17α-acetoxy-6-hydroxymethylpregna-4,6-diene-3,20-dione, and 17α-acetoxy-2α-hydroxy-6-hydroxymethylpregna-4,6-diene-3,20-dione. The major route of elimination of megestrol appears to be urinary excretion.121 Following oral administration of 4-90 mg of radiolabeled megestrol acetate, about 66% (range: 57-78%) of the dose was excreted in urine and about 20% (range: 8-30%) of the dose was excreted in feces within 10 days. About 5-8% of a dose is excreted in urine as identified metabolites.121
Megestrol acetate is a synthetic progestin which differs structurally from progesterone only in the addition of a 6-methyl group on the B ring, a 17-acetoxy group on the D ring of the steroid nucleus, and the addition of a 6-7 double bond. Megestrol acetate occurs as a white to creamy white, tasteless and essentially odorless, crystalline powder and is insoluble in water (solubility of the drug is 2 mcg/mL in water at 37°) and sparingly soluble in alcohol. Megestrol acetate is commercially available as oral tablets120 and as oral suspensions;121 the 2 concentrations of the oral suspensions differ in formulation and are not bioequivalent.138
Megestrol acetate tablets should be stored in well-closed containers at a temperature less than 40°C, preferably between 15-30°C and megestrol acetate oral suspension should be stored in tight containers at a temperature of 25°C or less.
Additional Information
For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Suspension | 200 mg/5 mL* | ||
Megestrol Acetate Suspension | ||||
625 mg/5 mL | Megace® ES | |||
Tablets | 20 mg* | Megestrol Acetate Tablets | ||
40 mg* | Megestrol Acetate Tablets |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Only references cited for selected revisions after 1984 are available electronically.
2. Mead Johnson. Megace® (megestrol acetate) prescribing information. Evansville, IN; 1971 Dec.
24. Cooper JM, Kellie AE. The metabolism of megestrol acetate (17α-acetoxy-6-methylpregna-4,6-diene-3,20-dione) in women. Steroids . 1968; 11:133-49. [PubMed 5636707]
100. Tchekmedyian NS, Tait N, Moody M et al. Appetite stimulation with megestrol acetate in cachectic cancer patients. Semin Oncol . 1986; 13(4 Suppl 4):37-43. [PubMed 3798127]
101. Tchekmedyian NS, Tait N, Moody M et al. High-dose megestrol acetate: a possible treatment for cachexia. JAMA . 1987; 257:1195-8. [PubMed 3806918]
102. Von Roenn JH, Murphy RL, Weber KM et al. Megestrol acetate for treatment of cachexia associated with human immunodeficiency virus (HIV) infections. Ann Intern Med . 1988; 109:840-1. [PubMed 3190032]
103. Aisner J, Tchekmedyian NS, Tait N et al. Studies of high-dose megestrol acetate: potential applications in cachexia. Semin Oncol . 1988; 15(2 Suppl 1):68-75. [PubMed 3285486]
104. Furth PA. Megestrol acetate and cachexia associated with human immunodeficiency virus (HIV) infection. Ann Intern Med . 1989; 110:667. [PubMed 2535614]
105. Von Roenn JH, Murphy RL, Weber KM et al. Megestrol acetate and cachexia associated with human immunodeficiency virus (HIV) infection. Ann Intern Med . 1989; 110:667-8. [PubMed 2535614]
106. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97-414), to June 30, 1993. Rockville, MD; 1993 Aug.
107. Fessel WJ. Megestrol acetate and hyperpnea. Ann Intern Med . 1989; 110:1034-5. [PubMed 2729805]
108. Schacter L, Rozencweig M, Canetta R et al. Megestrol acetate: clinical experience. Cancer Treat Rev . 1989; 16:49-63. [PubMed 2471590]
109. Hamburger AW, Parnes H, Gordon GB et al. Megestrol acetate-induced differentiation of 3T3-L1 adipocytes in vitro. Semin Oncol . 1988; 15(2 Suppl 1):76-8. [PubMed 2453082]
110. Aisner J, Tchekmedyian NS, Moody M et al. High-dose megestrol acetate for the treatment of advanced breast cancer: dose and toxicities. Semin Hematol . 1987; 24(2 Suppl 1):48-55. [PubMed 3589708]
111. Torti FM, Dieckmann B, Beutler B et al. A macrophage factor inhibits adipocyte gene expression: an in vitro model of cachexia. Science . 1985; 229:867-9. [PubMed 3839597]
112. Miksicek R, Heber A, Schmid W et al. Glucocorticoid responsiveness of the transcriptional enhancer of Moloney murine sarcoma virus. Cell . 1989; 46:283-90.
113. Muss HB, Wells HB, Paschold EH et al. Megestrol acetate versus tamoxifen in advanced breast cancer: 5-year analysis—a phase III trial of the Piedmont Oncology Association. J Clin Oncol . 1988; 6:1098-106. [PubMed 3292710]
114. Tchekmedyian NS, Tait N, Abrams J et al. High-dose megestrol acetate in the treatment of advanced breast cancer. Semin Oncol . 1988; 15(2 Suppl 1):44-9. [PubMed 3368800]
115. Reviewer's comments (personal observations). 1989 Dec 28.
116. Loprinzi CL, Ellison NM, Schaid DS et al. Controlled trial of megestrol acetate for the treatment of cancer anorexia and cachexia. J Natl Cancer Inst . 1990; 82:1127-32. [PubMed 2193166]
117. Heckmayr M, Gatzemeier U. Megestrol acetate in cachectic patients with advanced bronchogenic cancer. Onkologie . 1990; 13:285-7. [PubMed 2172885]
118. Bruera E, Macmillan K, Kuehn N et al. A controlled trial of megestrol acetate on appetite, caloric intake, nutritional status, and other symptoms in patients with advanced cancer. Cancer . 1990; 66:1279-82. [PubMed 2205358]
119. Raub W. Possible antianorexia/cachexia therapy for cancer patients. JAMA . 1990; 264:1086. [PubMed 2117074]
120. Megace® prescribing information. In: Barnhart ER, publisher. Physicians' desk reference. 44th ed. Oradell, NJ: Medical Economics Company Inc; 1990:749.
121. Mead Johnson. Megace® oral suspension (megestrol acetate) prescribing information. Princeton, NJ; 1993 Sep.
122. Oster M, Enders S, Samuels S et al. Randomized, double-blind study comparing high-dose megestrol acetate and placebo in cachectic patients with acquired immunodeficiency syndrome (AIDS). Int Conf AIDS . 1993; 9:528.
123. Berman S, Katz K, Ho M et al. Megestrol acetate produces weight gain in HIV+ patients. Int Conf AIDS . 1993; 9:499.
124. Von Roenn JH, Roth EL, Craig R. HIV-related cachexia: potential mechanisms and treatment. Oncology . 1992; 49(Suppl 2):50-4. [PubMed 1461629]
125. Scevola D, Bottari G, Oberto L et al. Changes in caloric intake, anthropometric parameters and TNF levels induced by megestrol acetate in AIDS patients. Int Conf AIDS . 1992; 8:133.
126. Flynn N, Enders S, Oster M etal. Megestrol acetate 800 mg/day vs placebo for treatment of weight loss and anorexia in AIDS patients. Int Conf Aids . 1992; 8:B205.
127. Mahayni H, Minor JR. Megestrol acetate in AIDS-related cachexia. Am J Hosp Pharm . 1991; 48:2479-80. [PubMed 1746586]
128. Von Roenn J, Roth E, Murphy R et al. Controlled trial of megestrol acetate for the treatment of AIDS-related anorexia and cachexia. Int Conf AIDS . 1991; 7:280.
129. Scevola D, Barbarini G, Bottari G et al. Prevalence, etiology and management of AIDS malnutrition. Int Conf AIDS . 1991; 7:224.
130. Tierney A, Cuff P, Kotler DP. The effect of megestrol acetate (Megace) on appetite, nutritional repletion, and quality of life in AIDS cachexia. Int Conf AIDS . 1991; 7:247.
131. Nathwani D, Green ST, Heslop JM et al. Beneficial response to megoestrol acetate in AIDS-related cachexia and a possible megoestrol withdrawal-associated syndrome? Acta Der Venereol (Stockh) . 1990; 70:520-1.
132. Von Roenn JH, Murphy RL, Wegener N. Megestrol acetate for treatment of anorexia and cachexia associated with human immunodeficiency virus infection. Semin Oncol . 1990; 17(Suppl 9):13-6. [PubMed 2259923]
133. Von Roenn JH, Murphy RL, Weitzman S. Megestrol acetate and the treatment of HIV-related cachexia. Proc Ann Meet Am Soc Clin Onco . 1988; 7:A17.
134. Nelson JE. “Pilot” studies. Ann Intern Med . 1989; 111:188-9. [PubMed 2742256]
135. Tchekmedyian NS. Clinical approaches to nutritional support in cancer. Curr Opin Oncol . 1993; 5:633-8. [PubMed 8364079]
136. Henry K, Rathgaber S, Sullivan C et al. Diabetes mellitus induced by megestrol acetate in a patient with AIDS and cachexia. Ann Intern Med . 1992; 116:53-4. [PubMed 1727096]
137. Bristol Myers Squibb, Princeton, NJ: personal communication.
138. Bristol Myers Squibb. Megace® ES (megestrol acetate) suspension prescribing information. Spring Valley, NY; 2005 May.