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Gynaecological Oncology
Chemotherapy for Early-stage High-risk Endometrial Cancer
Thomas Hogberg
Head, Department of Cancer Epidemiology, Lund University Hospital
Abstract
Endometrial cancer generally has a good prognosis because most cases are diagnosed in stage I. It is possible to identify subgroups of
patients with early-stage endometrial cancer with a poor prognosis. Despite a traditional generous use of adjuvant radiotherapy, these
patients have five-year overall survival of approximately 80%. In this group there is a need for an effective systemic adjuvant therapy. Mainly
based on superior response rates, doxorubicin + cisplatin was for many years the standard chemotherapy in endometrial cancer. GOG-177
was the first phase III study on chemotherapy in endometrial cancer that showed a survival advantage. Paclitaxel + doxorubicine + cisplatin
was better than doxorubicine + cisplatin, but the toxicity of the three-drug regimen has precluded general acceptance. Paclitaxel +
carboplatin has produced high response rates and is widely used, despite the lack of evidence based on randomised studies. GOG-122
compared doxorubicine + cisplatin with whole abdominal radiotherapy in advanced optimally operated endometrial cancer and showed
that chemotherapy with doxorubicine + cisplatin resulted in superior survival. Two recent studies have compared adjuvant chemotherapy
(cyclophosphamide + doxorubicine + cisplatin) with adjuvant radiotherapy in early-stage endometrial cancer. Both studies failed to show
a difference between the treatments. Another study (NSGO-EC-9501/EORTC-55991) compared adjuvant radiotherapy plus chemotherapy
with adjuvant radiotherapy, and showed better survival with the sequential combination.
Keywords
Adjuvant, chemotherapy, endometrial neoplasms, micrometastases, review
Disclosure: The author has no conflicts of interest to declare.
Received: 22 January 2009 Accepted: 30 March 2009
Correspondence: Thomas Hogberg, Onkol Centrum, Universitetssjukhuset, 221 85, Lund, Sweden. E:
thomas.hogberg@med.lu.se
Endometrial cancer (EC) is the most common gynaecological cancer [EORTC 55872] and Gynecologic Oncology Group [GOG-107]) have
in the developed world, and in 2002 it was estimated that worldwide compared doxorubicin and cisplatin (AP) with doxorubicin.
9,10
Both
around 200,000 women were diagnosed with the disease.
1
In Sweden, studies found that the combination gave better response rates but no
between 1970 and 2006 the age-standardised incidence increased by significant differences in survival. AP has for many years been
37%, but because of an ageing population the number of cases regarded as the standard in EC. In GOG-122 a taxane combination
increased by 80% during the same period.
2
EC has a good prognosis, (paclitaxel, doxorubicin, cisplatin [TAP]) was compared with AP in 273
but per stage it is about the same as for ovarian cancer.
3
In (263 eligible) women with advanced or recurrent EC of any cell type.
11
International Organization for Gynaecology and Obstetrics (FIGO) Response rate (RR), OS and progression-free survival (PFS) were
stage I there are subgroups with a high risk of micrometastatic significantly better with TAP. However, the toxicity of this regimen may
disease. For example, patients with stage IC grade 3 disease have 79% have precluded its use in many centres. Paclitaxel–carboplatin (TcP) is
five-year overall survival (OS) despite liberal use of adjuvant a commonly used drug combination in gynaecological cancer. Apart
radiotherapy (RT).
3
Four large trials have randomised patients to from its neurotoxicity, it is a well tolerated and manageable regimen.
adjuvant pelvic RT or observation after surgery.
4–7
All four failed to Phase II studies in EC have demonstrated high RR (60–70%).
8,12
show an improvement in OS, despite the fact that RT prevented up to Currently, two large randomised studies with TcP in the experimental
80% of progressions in the irradiated field. Thus, most patients arm are running: GOG-209 and Japanese Gynecologic Oncology Group
harbouring micrometastatic disease also have dissemination outside (JGOG)-2043.
13,14
It will be some years before we know the results.
the irradiated field and there is a need for systemic adjuvant therapy, Despite the lack of evidence based on randomised studies, TcP is
either added to or instead of RT. considered by many as the de facto standard.
Chemotherapy in Advanced or Gynecologic Oncology Group-122
Recurrent Endometrial Cancer GOG-122 was a pivotal study
15
that changed the way many considered
Phase II studies on chemotherapy (CT) in advanced or recurrent EC EC and CT. After surgical staging and optimal tumour resection (no
have shown response rates exceeding 20%, mainly with single site of residual tumour greater than 2cm), patients with FIGO
anthracyclines, platinum compounds and taxanes.
8
Two randomised stage III or IV EC of any histology were randomised to CT (doxorubicin
studies (European Organisation for Research and Treatment of Cancer 60mg/m
2
and cisplatin 50mg/m
2
every three weeks for seven cycles,
© TOUCH BRIEFINGS 2009 65
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