title: A randomized study comparing standard versus moderately high dose megestrol acetate for patients with advanced prostate carcinoma: cancer and leukemia group B study 9181.
abstract: BACKGROUND
  Megestrol acetate (MA) is a synthetic progestin with reported activity in both hormone-sensitive and hormone-refractory prostate carcinoma (HRPC). Based on limited data suggesting a possible dose-response effect, a trial was initiated to compare standard versus moderately high dose MA in HRPC.
  
  
  METHODS
  One hundred forty-nine men with hormone-refractory prostate carcinoma were randomized to receive oral MA either at 160 mg/day (low dose) or 640 mg/day (high dose). Patients were stratified by performance status and measurable versus evaluable disease. The primary end point was tumor response. Secondary end points were survival, quality-of-life measures, and prostate specific antigen (PSA) decline.
  
  
  RESULTS
  The median survival times of 11.2 months for patients who received the low dose and 12.1 months for patients who received the high dose therapy were not significantly different. Best response was equivalent in the 2 arms: 2 partial responses and 22 patients with stable disease for the 160 mg/day dose, and 1 partial response and 28 patients with stable disease for the 640 mg/day dose. A greater than 50% decline in PSA occurred in 13.8% and 8.8% of patients in the low and high dose treatment arms, respectively. There were no differences in the toxicity or quality-of-life outcomes between the two arms. Poorer performance status (2 vs. 0-1), greater than 5% weight loss, higher baseline PSA, and measurable disease all predicted shorter survival.
  
  
  CONCLUSIONS
  MA has limited activity in hormone-refractory prostate carcinoma, and there is no apparent dose-response correlation.
authors.affiliation: Walter Reed Army Medical Center, Washington, DC, USA.
authors.forename: N A
authors.initials: NA
authors.lastname: Dawson
authors.forename: M
authors.initials: M
authors.lastname: Conaway
authors.forename: S
authors.initials: S
authors.lastname: Halabi
authors.forename: E P
authors.initials: EP
authors.lastname: Winer
authors.forename: E J
authors.initials: EJ
authors.lastname: Small
authors.forename: D
authors.initials: D
authors.lastname: Lake
authors.forename: N J
authors.initials: NJ
authors.lastname: Vogelzang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000556:secondary; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D019290:Megestrol Acetate / Q000008:administration & dosage* / Q000009:adverse effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011788:Quality of Life; D015996:Survival Rate
chemical_list: D018931:Antineoplastic Agents, Hormonal; D019290:Megestrol Acetate