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Q: Second-line chemotherapy regimens for endometrial cancer ( Answered 3 out of 5 stars,   0 Comments )
Subject: Second-line chemotherapy regimens for endometrial cancer
Category: Health > Conditions and Diseases
Asked by: cstavaru-ga
List Price: $20.00
Posted: 30 Sep 2005 15:35 PDT
Expires: 30 Oct 2005 14:35 PST
Question ID: 574772
I want to know which are the most successful two or three ( in terms
of time to progression, overall survival and response ratio )
second-line chemotherapy regimens for metastatic endometrial cancer
following a first-line regimen that includes paclitaxel and
carboplatin. I want the treatment scheme for each regimen ( eg. how
much of each drug from the regimen is administered and when ).

Clarification of Question by cstavaru-ga on 30 Sep 2005 15:56 PDT
The cancer type I am searching an answer for is adenocarcinoma. I am
also interested in info about carcinosarcoma, but not for
leiomyosarcoma or sarcoma.
Subject: Re: Second-line chemotherapy regimens for endometrial cancer
Answered By: welte-ga on 01 Oct 2005 06:58 PDT
Rated:3 out of 5 stars
Hi cstavaru-ga, and thanks for your question.  My condolences if you
or an acquaintance has been diagnosed with this unfortunate disease. 
As usual, the following is not a substitute for medical advice or
direct medical evaluation and treatment.

One of the best resources for looking for evidence-based medicine
recommendation is the Cochrane
Database of Systematic Reviews.  The Database has a relevant entry:

Humber, C. Tierney, J. Symonds, P. Collingwood, M. Kirwan, J.
Williams, C. Green, J. Chemotherapy for advanced, recurrent or
metastatic endometrial carcinoma. [Systematic Review] Cochrane
Gynaecological Cancer Group Cochrane Database of Systematic Reviews.
3, 2005.

Here is the summary version of the above Systematic Review:

This review looked at 2288 patients between 1974 and 2000 who were
enrolled in 11 separate clinical trials.  For the studies that looked
at carboplatin in combination with paclitaxel, "Median survival was
reported by patient subgroup in this study; for recurrent
adenocarcinoma, the median survival was 15 months, whereas for newly
diagnosed advanced adenocarcinoma, median survival had not been
reached."  The review examined multiple chemotherapy agents used
solely or in combination, coming the the following conclusions:

"Recurrent, advanced or metastatic endometrial adenocarcinoma is
uncommon and rarely curable. In such a setting, it is desirable for
treatment to palliate symptoms, improve QOL [quality of life], prolong
time to disease progression and improve OS. The most rigorous method
of assessing the effectiveness of any treatment in achieving these
aims is to compare it with a "standard" treatment of known
effectiveness in a randomised controlled trial. Where no "standard"
treatment of known effectiveness exists, it may be acceptable to
compare the trial treatment with placebo or no treatment. In incurable
cancer, an acceptable control arm could be "Best Supportive Care"
(BSC) when it is not known if a treatment will definitely palliate
symptoms or prolong life."

The authors go on to discuss single vs. combination regimens:

"Response rates varied between RCTs [randomized controlled trials],
with the worst rates in the most heavily pre-treated patients
(Pawinski 1999, Edmonson 1987). In a number of trials, combination
therapy led to a higher response rate than single agent treatment or
other combination (Aapro 2003; Long 1995a; Thigpen 1994), but, with
the exception of Fleming 2004a, this better response rate did not
translate into better PFS [progression free survival] or OS [overall
survival], at least at the individual trial level. A meta-analysis of
the 6 trials that compared more intense chemotherapy combinations
suggests that more intense chemotherapy significantly improves the
median PFS and possibly OS, by around 1 month. However, this seems to
be at the expense of increased serious toxicity."

Only one trial found improved progression free survival and overall survival:

"The only RCT that reported a significant improvement in PFS and
survival was that of doxorubicin, cisplatin and paclitaxel versus
doxorubicin and cisplatin (Fleming 2004a), with the benefit associated
with the paclitaxel based therapy. However, grade 3 or 4
thrombocytopenia and neurological toxicity were also significantly
greater with this regimen and there were 5 treatment-related deaths.
There was no good evidence from the RCTs comparing other chemoptherapy
regimens or scheduling, that any were superior in terms of improved
survival and PFS and/or reduced toxicity. The median OS varied from
approximately seven months to 15 months and median PFS varied from
seven weeks to eight months and these may reflect prior treatments and
stage of disease, as well as the effect of any particular regime."


The  Agency for Healthcare Research and Quality (AHRQ) maintains the
National Guideline Clearinghouse to provide treatment guidelines for a
wide variety of diseases.  Here's their page for advanced or recurrent
endometrial cancer:

The guidelines agree with (and are, in fact, partially based on) those
from the Cochrane database:

For women with advanced or recurrent endometrial cancer:

* Combination chemotherapy is favoured over single agent chemotherapy
because of higher response rates.
* Paclitaxel in combination with cisplatin/doxorubicin chemotherapy
improves both response rate and median survival; however, the use of
this three-drug combination is associated with increased toxicity.
* Hormonal therapy may be a therapeutic option for those patients with
minimal symptoms or non-life threatening advanced or recurrent
endometrial cancer.

For women with uterine papillary serous carcinoma:

* Evidence supporting or refuting various chemotherapy regimens for
uterine papillary serous carcinoma is limited.
* Patients should be encouraged to participate in randomized trials."

Hormonal therapy has also been investigated for treatment of
endometrial cancer, either alone or in combination with chemotherapy
agents.  So far, it appears that well-differentiated low grade tumors
are the most responsive.  Less well differentiated tumors are less
likely to express the receptors needed to respond to hormonal therapy.
 Here is a good summary of the current state of hormonal therapy, from
Emory Healthcare, which includes dosing and scheduling information:

eMedicine has an article that briefly mentions use of hormone therapy
vs. tamoxifen, near the middle of the page:

"Tamoxifen is an effective alternative when progestin therapy is
contraindicated (eg, coronary artery disease, breast cancer). A 75-80%
objective response occurs with estrogen and/or progesterone
receptor?positive tumors compared to less than 5% in the absence of
estrogen and/or progesterone receptor?positive tumors. Unfortunately,
the tumors that tend to have intra-abdominal metastases are high grade
and are less likely to be estrogen and/or progesterone
receptor?positive tumors (15-41%). In cases of advanced disease,
sending tissue, specifically from metastatic sites, for receptor
analysis is useful. Metastases are receptor positive in 25% of
metastatic tumors compared to 60% of primary tumors."

A newer treatment currently being investigated is Topotecan.  Here is
a recent study looking at this type of therapy that showed antitumor
activity, even in patients with multiple prior treatments:

Traina TA. Sabbatini P. Aghajanian C. Dupont J. Weekly topotecan for
recurrent endometrial cancer: a case series and review of the
literature. [Review] [35 refs] [Case Reports. Journal Article. Review.
Review, Multicase] Gynecologic Oncology. 95(1):235-41, 2004 Oct.
UI: 15385138

Although not freely available online, you can request a reprint of
this article from Dr.  Dupont at Memorial Sloan-Kettering Cancer

Here are the results of their study, including treatment dosing and schedule:

"Eleven patients were treated with weekly topotecan during the study
period, with doses ranging from 2.5?4.0 mg/m2 on a 2- or 3-week
schedule with 1 week off. The median age of the patients was 60 years
old (range, 47?76 years), and the median Karnofsky performance status
was 80%. Six of the 11 patients were previously treated with more than
three chemotherapy regimens and eight had received prior pelvic
radiation. Ninety-seven percent of treatment doses were delivered as
scheduled, and only two patients required dose reductions. One patient
achieved a prolonged partial response for 54 weeks, and two patients
had stabilization of disease for 15 weeks each."

This type of treatment looks promising, but needs to be evaluated in
more patients in a prospective clinical trial before it will become a
part of the standard treatment guidelines.

So, there are very little efficacy of second line chemotherapy agents
that are routinely used in current medical practice.  The best reviews
of the literature encourage participation in clinical trials.

Here is a link to a continuously updated list of all currently active
clinical trials for treatment of endometrial cancer, which will point
you to detailed descriptions, contact information, etc.:

Not all of these results are relevant (for example, some are looking
at prevention of endometrial cancer in those with genetic
predisposition for the disease), so you can click on
"Search-Within-Results" near the top of the page and add another term,
such as "recurrent."  You can also click on "Map of Locations" to see
where all of these studies are located.  A small number of the studies
do not have location data and therefore won't show up on the map, so I
wouldn't use the map as the sole means of searching through the


To summarize, there are no good, proven second line chemotherapy
regimens, however some agents, discussed above, are being investigated
in clinical trials.  The current recommendation is for patients with
recurrent endometrial cancer to consider participation in these
clinical trials.  The most common chemotherapy regimens are available
below.  At this point, no firm distinction is made between treatment
of carcinocarcinoma (the most common type) and adenocarcinoma.  Here
is more information on the types, incidence, and prevalence of the


Additional resources:

Here is the eMedicine page on endometrial cancer, which has some
limited information on medical treatment options:

You can find specifics of dosing and scheduling of the various
chemotherapy regimens, along with references, here:

CAP (cytoxan, adriamycin, cisplatin)

PAC (cisplatin, adriamycin, cytoxan)

VACF (vincristine, adriamycin, cytoxan, 5-FU)


I hope this information was useful.  I wish you the best if you are
personally involved in this difficult struggle.  Please feel free to
request any clarification.


Search terms:
endometrial cancer, chemotherapy, regimens, recurrent

Google, eMedicine, Cochrane Database, National Guideline Clearinghouse

Request for Answer Clarification by cstavaru-ga on 01 Oct 2005 07:15 PDT
I'm surprised there is nothing on gemcitabine and docetaxel. I
remember reading ( newer articles ) about this combination for
endometrial cancer.

Clarification of Answer by welte-ga on 01 Oct 2005 11:04 PDT
Hi again cstavaru-ga,

I apologize for not being more clear... 

While the discussion I presented may seem somewhat dated, it
represents the currently accepted treatment protocol for recurrent
endometrial cancer.  Unfortunately, there are no good proven second
line treatment regimens available, so the current recommendation is to
consider participation in clinical trials.  More on this later...

Visiting the site I mentioned:

shows multiple trials at various phases that are currently recruiting
patients.  Here's one from that page that is using gemcitabine (with
or without docetaxel) as second-line therapy for recurrent or
persistent endometrial cancer.  Here's a direct link to this trial:;jsessionid=FAFC81655DC672E68C96E60C4FDAE836?order=11

Another trial from the page I cited is looking at thalidomide:;jsessionid=FAFC81655DC672E68C96E60C4FDAE836?order=12

Here is another trial looking at hormone therapy:;jsessionid=FAFC81655DC672E68C96E60C4FDAE836?order=14

These trials combines chemotherapy with whole body hyperthermia:;jsessionid=FAFC81655DC672E68C96E60C4FDAE836?order=33;jsessionid=FAFC81655DC672E68C96E60C4FDAE836?order=35

This trial is looking at Trastuzumab (Herceptin):

Here are some additional trials from the same source:

Fulvestrant in Treating Patients With Recurrent, Persistent, or
Metastatic Endometrial Cancer:

Combination Chemotherapy in Treating Patients With Stage III, Stage
IV, or Recurrent Endometrial Cancer

CCI-779 in Treating Patients With Metastatic or Locally Advanced
Recurrent Endometrial Cancer

Pemetrexed Disodium in Treating Patients With Persistent or Recurrent
Endometrial Cancer

RAD001 in Recurrent Endometrial Cancer

Ixabepilone in Treating Patients With Recurrent or Persistent Endometrial Cancer

Lapatinib in Treating Patients With Recurrent or Persistent Endometrial Cancer

AP23573 in Female Adult Patients with Recurrent or Persistent Endometrial Cancer

Again, I would periodically check the top level link above for new studies.  

Unfortunately, one cannot state that any of these medications,
including imatinib, gemcitabine, and docetaxel are helpful or harmful
for recurrent endometrial cancer until the final Phase trials are
complete and the data is analysed.  Any information you might find
that states that these agents definitively work for this disease would
have to be classified as unreliable, and I therefore did not focus on
them.  While the current treatment regimens may be ineffective, the
newer agents hypothesized to work have not been proven to work and may
in fact be harmful.

There are a few small studies out there discussing the use of these
agents in people, animals, and in cell culture, but these are not
sufficient to determine their overall efficacy and safety.  This is
why the current recommendation from multiple groups is to participate
in clinical trials, with the hope that you would be in an arm of the
trial receiving the most beneficial regimen, which at the time could
not be known.  Fortunately, there are quite a few clinical trials that
are currently recruiting patients, in part because this is such a
serious and difficult to treat disease.

Please feel free to request any additional clarification.

cstavaru-ga rated this answer:3 out of 5 stars
The answer focuses on information that is a little too old in my
opinion. Very little of the new drugs like imatinib, Gemcitabine,
Docetaxel, are brought into discussion. Of course, there is little
information about these and endometrial cancer giving that they are
new, but it can be found. In searching for information about such
serious diseases, the search should focus on the latest research and
studies, and only then to focus on the "traditional" and non-efficient

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