Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Closed	over 18	NCI	EST-2185

Objectives

I.  Determine whether pretreatment with premarin will increase the response 
rate and the time to treatment failure in ER-positive patients with metastatic 
breast adenocarcinoma treated with megestrol acetate.

Entry Criteria

Disease Characteristics:

See General Eligibility Criteria

Patient Characteristics:

See General Eligibility Criteria

General Eligibility Criteria:

Postmenopausal female patients with 
histologically documented measurable or evaluable progressive, inoperable, 
recurrent, or metastatic adenocarcinoma of the breast, provided they are not 
candidates for protocols of higher priority and have not received prior 
treatment with megestrol acetate or premarin.  The ECOG performance status 
must be 0-2, and liver and kidney function must be adequate as indicated by a 
bilirubin of not greater than 3 mg/dl and creatinine not greater than 1.5 
mg/dl and/or BUN not greater than 30.  Postmenopausal status must be 
established according to one of the following:  physiologic or chemical 
menopause must have occurred at least 1 year prior to entry; surgical 
castration must have occurred at least 8 weeks prior to entry, followed by 
progression of disease; patients over the age of 52 years must have undergone 
hysterectomy; or patients must have been continuously amenorrheic for more 
than 12 months secondary to radiotherapy or systemic chemotherapy.  Patients 
must be ER-positive; progesterone receptor levels should be obtained if 
possible.  The following are not acceptable as measurable or evaluable 
lesions:  pleural effusion; pure osteoblastic or mixed osteolytic/osteoblastic 
lesions that do not require analgesics; lesions within the field of prior 
radiotherapy unless they demonstrate current evidence of progressive disease.  
There may have been no prior treatment with estrogens or MEG for breast 
cancer.  Patients who have received previous exogenous hormone or antihormone 
therapy must satisfy one of the following criteria:  treatment was for 12 
weeks or less and was associated with symptomatic or objective progression or 
with relapse after withdrawal response; treatment (not including tamoxifen) 
was for more than 12 weeks, the drug was stopped for a minimum of 7 days, and 
this withdrawal period was associated with either no improvement, progression, 
or relapse after withdrawal response; treatment included tamoxifen, was 
administered for more than 12 weeks, the drug was stopped for at least 14 
days, and this withdrawal period was associated with objective progression or 
with relapse after withdrawal response; or treatment included tamoxifen, was 
administered for more than 12 weeks, the drug was stopped for a minimum of 28 
days, and this withdrawal period was associated with no improvement or with 
relapse after withdrawal response.  Patients may have received a maximum of 
one prior nonhormonal chemotherapeutic regimen, but they must have recovered 
from the toxic effects of such therapy prior to entry.  Patients who develop 
recurrent disease at more than 6 months after completion of systemic adjuvant 
therapy are eligible, but patients who develop recurrent breast cancer within 
6 months of completing adjuvant systemic therapy will be considered as having 
failed their first regimen for metastatic disease.  Patients who received 
prior radiotherapy for the treatment of breast cancer with osseous lesions are 
eligible provided the previously treated area now shows evidence of recurrent 
or progressive disease or is not the only evaluable/measurable site of 
disease.  There may have been not more than one prior hormonal or 
chemotherapeutic regimen for metastatic cancer, and patients must not have 
undergone prior surgical adrenalectomy or hypophysectomy.  There may be no 
history of malignant neoplasm aside from curatively treated basal cell or 
squamous cell carcinoma of the skin or cured carcinoma of the cervix 
(exceptions to this requirement may be discussed with the study chairman).  
Patients must be free from active peptic ulcer, uncontrolled congestive heart 
failure, uncontrolled diabetes mellitus, hypertension with diastolic pressure 
regularly above 100 mm Hg, and psychiatric illness that would preclude 
protocol treatment.  At the time of entry, patients must not have CNS 
metastases, lymphangitic pulmonary metastases, or peritoneal metastases with 
ascites.

Expected Enrollment

287 patients will be entered over about 3 years.

Outline

Randomized study.
Arm I:  Single-agent Progestin Therapy.  Megestrol acetate, MEG, NSC-71423.
Arm II:  Single-agent Estrogen Therapy Followed by Single-agent Progestin 
Therapy.  Premarin; followed by MEG.

Cobau CD, Declercq K, Neuberg D, et al.: A randomized trial of megestrol acetate with or without premarin in the treatment of potentially responsive metastatic breast cancer. A Study of the Eastern Cooperative Oncology Group (E2185). Cancer 77 (3): 483-9, 1996.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Charles Cobau, MD, Protocol chair		Ph: 419-479-5605