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)

Charles D. Cobau, Katrien Declercq, Donna Neuberg, James N. Ingle, Douglass C. Tormey

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

BACKGROUND. Human breast cancer cells in vitro exhibit increased levels of progestin receptors (PgR) after brief exposure to physiologic concentrations of estrogens. Prior clinical studies have positively correlated the responsiveness of metastatic breast cancer to progestin therapy with the level of PgR in the tumor cells. METHODS. These observations were used as the scientific basis for a randomized clinical trial by the Eastern Cooperative Oncology (ECOG) to compare the effectiveness of megestrol acetate (MEG) alone in a daily dose of 160 mg with MEG alternated with premarin in a dose of 1.25 mg/day on the first 3 days of a 14 day cycle (PRE/MEG). From 1985 through 1989, 266 eligible and fully evaluable patients were randomized to 1 of the treatment arms and accrued to this trial. All patients were postmenopausal with biochemical estrogen cytosol protein receptor (ER) positive (≥ 10 fm/mg) tumors. The treatment groups were balanced with respect to performance status, number of involved organ systems, and PgR levels. RESULTS. Forty- five of 1135 (95% confidence interval [CI], 25-42% patients receiving MEG experienced a partial (PR) or complete (CR) response. Thirty-one of 131 (23%) (95% CI, 17-32%) patients receiving PRE/MEG achieved a PR or CR. Survival was not influenced by treatment selection. However, median time to progression was seven months for patients receiving MEG and four months for the group receiving PRE/MEG (P = 0.03). The treatment failure hazard rate was higher for patients with a short disease free interval after primary treatment of the breast cancer, poor performance status, non-white race, and visceral disease. Survival was negatively impacted by short disease free interval, administration of prior radiation therapy, prior treatment for metastatic disease, and hepatic involvement. CONCLUSIONS. Sequential treatment with premarin and megestrol acetate is not superior to treatment with megace alone in potentially hormone responsive patients with advanced breast cancer.

Original languageEnglish (US)
Pages (from-to)483-489
Number of pages7
JournalCancer
Volume77
Issue number3
DOIs
StatePublished - Feb 1 1996

Fingerprint

Megestrol Acetate
Conjugated (USP) Estrogens
Breast Neoplasms
Progesterone Receptors
Therapeutics
Confidence Intervals
Survival
Progestins
Treatment Failure
Cytosol
Neoplasms
Estrogens
Radiotherapy
Randomized Controlled Trials
Hormones

Keywords

  • breast cancer
  • hormone responsive
  • megace
  • metastatic
  • premarin
  • randomized trial
  • treatment

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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). / Cobau, Charles D.; Declercq, Katrien; Neuberg, Donna; Ingle, James N.; Tormey, Douglass C.

In: Cancer, Vol. 77, No. 3, 01.02.1996, p. 483-489.

Research output: Contribution to journalArticle

Cobau, Charles D. ; Declercq, Katrien ; Neuberg, Donna ; Ingle, James N. ; Tormey, Douglass C. / 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). In: Cancer. 1996 ; Vol. 77, No. 3. pp. 483-489.
@article{d713f21a7748451ba784e233053072b3,
title = "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)",
abstract = "BACKGROUND. Human breast cancer cells in vitro exhibit increased levels of progestin receptors (PgR) after brief exposure to physiologic concentrations of estrogens. Prior clinical studies have positively correlated the responsiveness of metastatic breast cancer to progestin therapy with the level of PgR in the tumor cells. METHODS. These observations were used as the scientific basis for a randomized clinical trial by the Eastern Cooperative Oncology (ECOG) to compare the effectiveness of megestrol acetate (MEG) alone in a daily dose of 160 mg with MEG alternated with premarin in a dose of 1.25 mg/day on the first 3 days of a 14 day cycle (PRE/MEG). From 1985 through 1989, 266 eligible and fully evaluable patients were randomized to 1 of the treatment arms and accrued to this trial. All patients were postmenopausal with biochemical estrogen cytosol protein receptor (ER) positive (≥ 10 fm/mg) tumors. The treatment groups were balanced with respect to performance status, number of involved organ systems, and PgR levels. RESULTS. Forty- five of 1135 (95{\%} confidence interval [CI], 25-42{\%} patients receiving MEG experienced a partial (PR) or complete (CR) response. Thirty-one of 131 (23{\%}) (95{\%} CI, 17-32{\%}) patients receiving PRE/MEG achieved a PR or CR. Survival was not influenced by treatment selection. However, median time to progression was seven months for patients receiving MEG and four months for the group receiving PRE/MEG (P = 0.03). The treatment failure hazard rate was higher for patients with a short disease free interval after primary treatment of the breast cancer, poor performance status, non-white race, and visceral disease. Survival was negatively impacted by short disease free interval, administration of prior radiation therapy, prior treatment for metastatic disease, and hepatic involvement. CONCLUSIONS. Sequential treatment with premarin and megestrol acetate is not superior to treatment with megace alone in potentially hormone responsive patients with advanced breast cancer.",
keywords = "breast cancer, hormone responsive, megace, metastatic, premarin, randomized trial, treatment",
author = "Cobau, {Charles D.} and Katrien Declercq and Donna Neuberg and Ingle, {James N.} and Tormey, {Douglass C.}",
year = "1996",
month = "2",
day = "1",
doi = "10.1002/(SICI)1097-0142(19960201)77:3<483::AID-CNCR9>3.0.CO;2-L",
language = "English (US)",
volume = "77",
pages = "483--489",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "3",

}

TY - JOUR

T1 - A randomized trial of megestrol acetate with or without premarin in the treatment of potentially responsive metastatic breast cancer

T2 - A study of the Eastern Cooperative Oncology Group (E2185)

AU - Cobau, Charles D.

AU - Declercq, Katrien

AU - Neuberg, Donna

AU - Ingle, James N.

AU - Tormey, Douglass C.

PY - 1996/2/1

Y1 - 1996/2/1

N2 - BACKGROUND. Human breast cancer cells in vitro exhibit increased levels of progestin receptors (PgR) after brief exposure to physiologic concentrations of estrogens. Prior clinical studies have positively correlated the responsiveness of metastatic breast cancer to progestin therapy with the level of PgR in the tumor cells. METHODS. These observations were used as the scientific basis for a randomized clinical trial by the Eastern Cooperative Oncology (ECOG) to compare the effectiveness of megestrol acetate (MEG) alone in a daily dose of 160 mg with MEG alternated with premarin in a dose of 1.25 mg/day on the first 3 days of a 14 day cycle (PRE/MEG). From 1985 through 1989, 266 eligible and fully evaluable patients were randomized to 1 of the treatment arms and accrued to this trial. All patients were postmenopausal with biochemical estrogen cytosol protein receptor (ER) positive (≥ 10 fm/mg) tumors. The treatment groups were balanced with respect to performance status, number of involved organ systems, and PgR levels. RESULTS. Forty- five of 1135 (95% confidence interval [CI], 25-42% patients receiving MEG experienced a partial (PR) or complete (CR) response. Thirty-one of 131 (23%) (95% CI, 17-32%) patients receiving PRE/MEG achieved a PR or CR. Survival was not influenced by treatment selection. However, median time to progression was seven months for patients receiving MEG and four months for the group receiving PRE/MEG (P = 0.03). The treatment failure hazard rate was higher for patients with a short disease free interval after primary treatment of the breast cancer, poor performance status, non-white race, and visceral disease. Survival was negatively impacted by short disease free interval, administration of prior radiation therapy, prior treatment for metastatic disease, and hepatic involvement. CONCLUSIONS. Sequential treatment with premarin and megestrol acetate is not superior to treatment with megace alone in potentially hormone responsive patients with advanced breast cancer.

AB - BACKGROUND. Human breast cancer cells in vitro exhibit increased levels of progestin receptors (PgR) after brief exposure to physiologic concentrations of estrogens. Prior clinical studies have positively correlated the responsiveness of metastatic breast cancer to progestin therapy with the level of PgR in the tumor cells. METHODS. These observations were used as the scientific basis for a randomized clinical trial by the Eastern Cooperative Oncology (ECOG) to compare the effectiveness of megestrol acetate (MEG) alone in a daily dose of 160 mg with MEG alternated with premarin in a dose of 1.25 mg/day on the first 3 days of a 14 day cycle (PRE/MEG). From 1985 through 1989, 266 eligible and fully evaluable patients were randomized to 1 of the treatment arms and accrued to this trial. All patients were postmenopausal with biochemical estrogen cytosol protein receptor (ER) positive (≥ 10 fm/mg) tumors. The treatment groups were balanced with respect to performance status, number of involved organ systems, and PgR levels. RESULTS. Forty- five of 1135 (95% confidence interval [CI], 25-42% patients receiving MEG experienced a partial (PR) or complete (CR) response. Thirty-one of 131 (23%) (95% CI, 17-32%) patients receiving PRE/MEG achieved a PR or CR. Survival was not influenced by treatment selection. However, median time to progression was seven months for patients receiving MEG and four months for the group receiving PRE/MEG (P = 0.03). The treatment failure hazard rate was higher for patients with a short disease free interval after primary treatment of the breast cancer, poor performance status, non-white race, and visceral disease. Survival was negatively impacted by short disease free interval, administration of prior radiation therapy, prior treatment for metastatic disease, and hepatic involvement. CONCLUSIONS. Sequential treatment with premarin and megestrol acetate is not superior to treatment with megace alone in potentially hormone responsive patients with advanced breast cancer.

KW - breast cancer

KW - hormone responsive

KW - megace

KW - metastatic

KW - premarin

KW - randomized trial

KW - treatment

UR - http://www.scopus.com/inward/record.url?scp=0030048427&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030048427&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1097-0142(19960201)77:3<483::AID-CNCR9>3.0.CO;2-L

DO - 10.1002/(SICI)1097-0142(19960201)77:3<483::AID-CNCR9>3.0.CO;2-L

M3 - Article

C2 - 8630955

AN - SCOPUS:0030048427

VL - 77

SP - 483

EP - 489

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 3

ER -