Hormonal therapy in advanced or recurrent endometrial cancer

Abstract

Background: Endometrial cancer is a cancer of the lining of the womb and worldwide is the seventh most common cancer in women. Treatment with hormones is thought to be beneficial in patients with endometrial cancer.

Objectives: To assess the indications, effectiveness and safety of hormone therapy for advanced or recurrent epithelial endometrial cancer.

Search strategy: We searched the Cochrane Gynaecological Cancer Group Trials Register, MEDLINE, EMBASE up to May 2009 and and CENTRAL (Issue 2, 2009). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies, and contacted experts in the field.

Selection criteria: Randomised controlled trials (RCTs) that studied hormonal therapy in adult women diagnosed with advanced or recurrent endometrial cancer.

Data collection and analysis: Two review authors independently abstracted data and assessed risk of bias. Comparisons were restricted to single-trial analyses so we did not synthesise data in meta-analyses.

Main results: We found six trials (542 participants) that met our inclusion criteria. These trials assessed the effectiveness of hormonal therapy in women with advanced or recurrent endometrial cancer as a single agent, as part of combination therapy and as low versus high dose. All comparisons were restricted to single-trial analyses, where we found no evidence that hormonal therapy as a single agent or as a combination treatment prolonged overall or five-year disease-free survival of women with advanced or recurrent endometrial cancer. However, low-dose hormonal therapy may have had a benefit in terms of overall and progression-free survival (PFS) compared to high-dose hormonal therapy (HR 1.31, 95% CI 1.04 to 1.66 and HR 1.35, 95% CI 1.07 to 1.71 for overall and PFS, respectively).

Authors' conclusions: We found insufficient evidence that hormonal treatment in any form, dose or as part of combination therapy improves the survival of patients with advanced or recurrent endometrial cancer. However, a large number of patients would be needed to demonstrate an effect on survival and none of the included RCTs had a sufficient number of patients to demonstrate a significant difference. In the absence of a proven survival advantage and the heterogeneity of patient populations, the decision to use any type of hormonal therapy should be individualised and with the intent to palliate the disease. It is debatable whether outcomes such as quality of life, treatment response or palliative measures such as relieving symptoms should take preference over overall and PFS as the major objectives of future trials.

Conflict of interest statement

None known.

Figures

1

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

2

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

1.1. Analysis

Comparison 1 MPA versus tamoxifen, Outcome 1 Death within 1 year.

2.1. Analysis

Comparison 2 CAF and MPA followed by tamoxifen versus CAF alone, Outcome 1 Death within 2 years.

3.1. Analysis

Comparison 3 Adjuvant progestagen therapy versus control, Outcome 1 Death within 5 years.

4.1. Analysis

Comparison 4 High‐dose MPA versus low‐dose MPA, Outcome 1 Overall survival.

4.2. Analysis

Comparison 4 High‐dose MPA versus low‐dose MPA, Outcome 2 Progression‐free survival.

4.3. Analysis

Comparison 4 High‐dose MPA versus low‐dose MPA, Outcome 3 Thrombophlebitis.

5.1. Analysis

Comparison 5 Megestrol and tamoxifen versus megestrol, Outcome 1 Death within 5 years.

6.1. Analysis

Comparison 6 OPC and radiotherapy versus radiotherapy alone, Outcome 1 5‐year disease‐free survival.

References

References to studies included in this review Ayoub 1988 {published data only}

Pandya 2001 {published data only} Rendina 1984 {published data only} Stolyarova 2001 {published data only} Thigpen 1999 {published data only} Urbanski 1993 {published data only} References to studies excluded from this review Behling 1983 {published data only} Bruera 1998 {published data only} Carey 2006 {published data only} Cohen 1984 {published data only} COSA trial {published data only} Decruze 2007 {published data only} Deng 2000 {published data only} Humber 2005 {published data only} Kneale 1988 {published data only} Krafft 1990 {published data only} Lentz 1996 {published data only} Lotze 1982 {published data only} Macdonald 1988 {published data only} Martin‐Hirsch 1996 {published data only} Martin‐Hirsch 1999 {published data only} Piver 1980 {published data only} Polyzos 2006 {published data only} Vavra 1990 {published data only} Vishnevsky 1993 {published data only} Zhang 1996 {published data only} References to ongoing studies Bloss {published data only} Additional references Aalders 1984 Ackerman 1996 Armstrong 1975 Asbury 2002 Berek 2005 Bonte 1981 Bucher 1997 Burke 2003 Carlson 1984 Chang 2008 Covens 1997 Covens 2003 CTCAE 2006 Decruze 2007 Deeks 2001 DerSimonian 1986 Edmonson 1986 Farquhar 2009 Fiorica 2004 Gallagher 1991 Geisler 1973 GLOBOCAN 2002 [Computer program] Hald 1983 Higgins 2003 Higgins 2008 Hill 1996 Hoffman 1989 Jemal 2008 Jeyarajah 1996 Jick 1979 Kaaks 2002 Kauppila 1984 Kelley 1965 Kitchener 2008 Kohorn 1976 Lentz 1996 Levine 1998 Lindemann 2008 Lovecchio 1984 Ma 2004 Markman 1997 Markman 2004 McMeekin 2003 Moore 1991 Obel 2006 Parmar 1998 Piver 1980 Piver 1986 Podratz 1985 Quinn 1989 Reifenstein 1974 Rose 2000 Sall 1979 Santin 2004 Sears 1994 Sehouli 2008 Singh 2007 Slavik 1984 Sohaib 2007 Swenerton 1979 Temkin 2009 Thigpen 1999 Thigpen 2001 Whitney 2004