Trial Information

Phase I/II Study of High-Dose Megestrol in Breast or Endometrial Carcinoma or Mesothelioma

OBJECTIVES: I. Evaluate the clinical effects of high-dose oral megestrol in improving
regression rate and prolonging survival in patients with breast or endometrial carcinoma or
mesothelioma. II. Evaluate the immune, endocrine, and clinical effects of this regimen, with
particular attention to effects on cachexia.

OUTLINE: This is a randomized study. Patients are stratified by performance status, dominant
site of disease, and prior treatment with megestrol. Breast cancer patients are randomized
to one of 3 doses of oral megestrol (800, 1,280, or 1,600 mg/day, divided qid). Female
patients with other tumor types are nonrandomly assigned to receive oral megestrol at 1,600
mg/day. Male patients are nonrandomly assigned to a dose-finding study of megestrol. The
first patient cohort receives megestrol at 480 mg/day in 3 divided doses, with further
escalation for subsequent cohorts as tolerated. All patients continue therapy for at least 8
weeks, with treatment discontinued upon progression. Measurable lesions are evaluated every
2 months.

PROJECTED ACCRUAL: 9 evaluable breast cancer patients at each dose level will be entered; 14
patients will be required for each of the other disease categories. (As of 11/92, the study
is temporarily closed to patients with prostate cancer.)