Evaluation dose-response characteristics of megestrol acetate in Thai patients with cancer anorexia-cachexia

Substantial number of cancer patients suffer from progressive weight loss, namely cancer anorexia-cachexia syndrome. Many palliative measures were used to alleviate this condition with some success. Megestrol acetate is a progestrogen which found to have effects on appetite and body weight. Previous studies used conventional to high dose of megestrol acetate, 160 milligram per day or over, and found megestrol could be effectively used to palliate cancer anorexia-cachexia. The precise mechanisms of action have not yet been elucidated. Nor was the appropriate starting dose encountered. This trial studied the effect of low dose, 40 milligrams per day, megestrol comparing to conventional dose. Twenty-eight patients were enrolled and completed the study. Eighteen males and 10 females were included. There were 17 lung cancers, 5 liver cancers, and 6 other cancer. Concurrent treatments with chemotherapy or radiotherapy were allowed. All patients had severe weight loss more than 10% of premorbid body weight. Patients were randomly allocated into two groups. At least 4 weeks duration of follow up was required. At the end of the study both 2 groups had lost body weight with mean of percent of body weight changes to be -2.48±4.8 in low dose arm and -1.98±5.1 in conventional dose arm. However 21.4% of patients in low dose arm had actual gain of body weight. Anthropometric measurements found decreased mid-arm circumference and triceps skinfold in conventional dose arm. The low dose arm had only decreased mid-arm circumference but not triceps skinfold. Appetite stimulating effect of megestrol was confirmed by quality of life questionnaire score. Overall quality of life assessment was slightly better in the conventional dose group than those of the low dose group. Patients in both arms had a better performance status at the end of study with more improvement in the 160 mg/d megestrol. There were more patients with weight loss when comparing concurrent treatment factors. Percent of patients with weight loss in concurrent treatment group was 46.2% whereas 13.3 % in no concurrent treatment group. There was trends of favorable responses in term of weight gain, appetite enhancement, quality of life, and performance status in the conventional dose arm. Although these did not reach statistical significance. Side effects were negligible. Conventional dose of megestrol acetate, 160 mg/d, should be more suitable starting dose than the lower dose.