Studies of high-dose megestrol acetate: potential applications in cachexia.
Cachexia can be a severe problem in the management of patients with cancer and other illnesses because it produces an ever-increasing spiral of anorexia, undernutrition, loss of tissue mass, muscle wasting, and increased susceptibility to infection and treatment toxicity. Megestrol acetate has been observed to produce weight gain in patients with hormone-sensitive tumors and has recently been noted to produce a similar degree of weight gain in those with hormone insensitive tumors. A review of our experience in a phase I-II study of escalating doses of megestrol acetate for advanced breast cancer revealed that weight gain occurred in more than 80% of all treated patients and in 90% of those patients who received treatment for 6 or more weeks. The median maximum weight gain was 5.5 kg, with a range of -5.6 to 44 kg. Subjective improvement in appetite occurred in most patients. These data provided the impetus for a series of further studies of the role of megestrol acetate in the control of cachexia, including a randomized study in cancer cachexia, AIDS cachexia, and anorexia nervosa. In addition, a number of laboratory trials seeking the mechanism of action have been initiated, as well as whole-animal studies to define the compartment of increased weight. Our data and the preliminary observation of weight gain in patients with hormone insensitive tumors suggest that megestrol acetate has a potential role in producing a possibly dose-related subjective improvement and an increase in appetite and weight. Further research is necessary to understand the mechanism of appetite stimulation and anabolic effect.
Aisner
J
J
University of Maryland, Cancer Center, Baltimore 21201.
Tchekmedyian
N S
NS
Tait
N
N
Parnes
H
H
Novak
M
M
D001835:Body Weight; D001943:Breast Neoplasms / Q000150:complications* / Q000188:drug therapy; D002100:Cachexia / Q000188:drug therapy* / Q000209:etiology; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D008535:Megestrol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019290:Megestrol Acetate
D008535:Megestrol; D019290:Megestrol Acetate