Prospective randomised trial of two dose levels of megestrol acetate in the management of anorexia-cachexia syndrome in patients with metastatic cancer.

Two doses of megestrol acetate (MA) have been prospectively compared in a random fashion as treatment for cancer-related anorexia-cachexia syndrome (ACS) in 122 patients with progressive soft tissue sarcoma, colorectal, lung, head and neck and renal cancer resistant to systemic chemotherapy. After 30 days of MA, 55% of patients receiving MA at 160 mg day-1 reported an increase in appetite, 27% of patients no variation and 18% complained of a decrease in appetite. Patients treated with MA at 320 mg day-1 reported an increase in appetite in 68% of cases, a stabilisation in 20% of cases and a decrease in 12%. Although an increase in appetite was more frequently observed in patients receiving MA at 320 mg day-1, however this difference was not statistically significant (P = 0.305). After 30 days of MA, 31% of patients treated with MA at 160 mg day-1 showed an increase in body weight, 25% a stabilisation and 44% a decrease. In the group of patients treated with MA at 320 mg day-1, 45% reported an increase in body weight, 16% no change and 23% weight loss. Although there was a trend favouring the higher dose of MA, overall analysis however failed to detect any statistically significant difference between the two treatment arms (P = 0.242). Twenty-seven patients pretreated with 160 mg day-1 and 23 patients treated with 320 mg day-1 received further therapy with MA at the dose of 320 and 480 mg day-1 respectively. In the group of 22 patients treated with 320 mg day-1 four (18%) reported an increase in body weight, eight (36%) an improvement in appetite, but none had an increase in performance status. Among the 20 evaluable patients treated with 480 mg day-1, two (10%) had an increase in body weight, four (20%) an improvement in appetite, but none reported an increase in performance status. No difference in median survival was detected between the two arms. Toxicity was mild and predictable. In conclusion, the data achieved in the present study confirm the clinical safety and effectiveness of oral MA in the management of ACS in patients with advanced cancer resistant to systemic chemotherapy. Moreover, data concerning the dose escalation of MA dosage in unresponsive patients suggest that a step by step increase in MA dosage could be the best way of administering MA for the management of ACS and that the increase of MA dosage over 480 mg day-1 will probably be useless in the vast majority of cases. Data on body weight suggest that after 2 weeks' therapy MA could be stopped or its dosage tailored to patients' needs since the majority of patients respond after only 15 days of MA.