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) and has been designated an orphan drug by the US Food and Drug Administration (FDA) for this use. 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. 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. Weight gain was associated with increases in nonwater body weight; edema developed or worsened in only 3 patients. 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. 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. Weight gain was associated with increases in nonwater body weight; edema was not reported in any of the patients receiving megestrol therapy. Increased appetite occurred in about 67% of patients receiving megestrol compared with 38% of those receiving placebo; however, daily caloric intake was similar in patients receiving megestrol and those receiving placebo.
Results of other controlled and uncontrolled 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, although some increases (mean increases of 69/ mm) in helper/inducer (CD4) T-cell counts have been reported occasionally. 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.
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. 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. 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. 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. 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. 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; however, some, but not all, evidence indicates that megestrol-induced weight gain may be dose-related.
Megestrol therapy generally has been well tolerated by most patients receiving the drug for the management of cachexia, and many patients with HIV infection or neoplastic disease have reported a subjective improvement in their sense of well-being during megestrol therapy. However, hyperpnea reportedly has occurred in at least 2 HIV-infected patients receiving 240 mg of the drug daily.
(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, and to determine the optimum dosage of megestrol for these conditions. In addition, some clinicians have mentioned theoretically the possible effects of megestrol's potential glucocorticoid action on HIV and the expression of HIV infection.
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.