PROSPECTIVE RANDOMIZED TRIAL OF 2 DOSE LEVELS OF MEGESTROL-ACETATE INTHE MANAGEMENT OF ANOREXIA-CACHEXIA SYNDROME IN PATIENTS WITH METASTATIC CANCER

Two doses of megestrol acetate (MA) have been prospectively compared i n a random fashion as treatment for cancer-related anorexia-cachexia s yndrome (ACS) in 122 patients with progressive soft tissue sarcoma, co lorectal, lung, head and neck and renal cancer resistant to systemic c hemotherapy. After 30 days of MA, 55% of patients receiving MA at 160 mg day(-1) reported an increase in appetite, 27% of patients no variat ion and 18% complained of a decrease in appetite. Patients treated wit h MA at 320 mg day(-1) reported an increase in appetite in 68% of cast s, a stabilisation in 20% of cases and a decrease in 12%. Although an increase in appetite was more frequently observed in patients receivin g 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 sta bilisation and 44% a decrease. In the group of patients treated with M A at 320 mg day(-1), 45% reported an increase in body weight, 16% no c hange and 23% weight loss. Although there was a trend favouring the hi gher dose of MA, overall analysis however failed to detect and statist ically significant difference between the two treatment arms (P = 0.24 2). Twenty-seven patients pretreated with 160 mg day(-1) and 23 patien ts treated with 320 mg day(-1) received further therapy with MA al the dose of 320 and 480 mp day(-1) respectively. In the group of 22 patie nts treated with 320 mg day(-1), four (18%) reported an increase in bo dy weight, eight (36%) an improvement in appetite, but none had an inc rease in performance status. Among the 20 evaluable patients treated w ith 480 mg day(-1), two (10%) had an increase in body weight, four (20 %) an improvement in appetite, but none reported an increase in perfor mance status. No difference in median survival was detected between th e two arms. Toxicity was mild and predictable. in conclusion, the data achieved in the present study confirm the clinical safety and effecti veness of oral MA in the management of ACS in patients with advanced c ancer resistant to systemic chemotherapy, Moreover, data concerning ti le dose escalation of MA dosage in unresponsive patients suggest that a step by step increase in MA dosage could be the best way of administ ering 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 c ases. Data on body weight suggest that after 2 weeks' therapy MA could be stopped or its dosage tailored to patients' needs since the majori ty of patients respond after only 15 days of MA.