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Q: Endometrial Cancer ( Answered,   1 Comment )
Question  
Subject: Endometrial Cancer
Category: Health > Conditions and Diseases
Asked by: microscope-ga
List Price: $22.50
Posted: 26 Apr 2003 15:52 PDT
Expires: 26 May 2003 15:52 PDT
Question ID: 195921
Question for Viola

Endometrial Cancer
I had surgery for endometrial cancer in August 2001. Staging was Grade
1, Stage 1B.
The cytology from the peritoneal washings came back “suspicious”. 
Because of the cytology results, my oncologist has me taking 160 mg of
Megace per day. Within six months of starting Megace, I gained 50
pounds and haven’t been able to take it off.
My oncologist tells me there is no real scientific evidence supporting
Megace for this purpose, but he knows it’s been prescribed for this
purpose in the past, and he would rather err on the side of caution.

My questions are: 
1) Can you find any scientific evidence why I should continue with
Megace?
2) Is there another way to deal with the “suspicious” cytology results
besides Megace?
3) Can I safely taper off Megace and not worry about a recurrence of
the cancer?
4) How have others who have taken Megace lose the weight after
discontinuing the drug?

Please cite the appropriate web sites that substantiate your research.

Thank You,
ruby

Request for Question Clarification by voila-ga on 26 Apr 2003 22:18 PDT
Hi Ruby,

Thanks for requesting me personally and I'll be happy to help with
your research.  I must confess that I'm somewhat of an "immersion"
researcher, so I hope you don't mind if I take some time with your
question.

Unfortunately, weight gain is #1 in the side effect profile for
Megace, but I'll see what information I can find for patients taking
or tapering off that drug.

Regards,
V
Answer  
Subject: Re: Endometrial Cancer
Answered By: voila-ga on 27 Apr 2003 17:30 PDT
 
Hello Ruby,

Your questions regarding endometrial cancer are important ones since
in the U.S. EC is the most common cancer of the female reproductive
organs.  It's fortunate that you were diagnosed in the early stages. 
Please note that the following research is not a substitute for
medical advice regarding your course of treatment.  No two physicans
will agree on any singular plan of care and second opinions are always
recommended and encouraged.

Before I approach your specific questions, I'd like to give you a bit
of background on your diagnosis and the use of Megace as part of your
treatment plan.

======================
PER NIH
======================
http://www.nlm.nih.gov/medlineplus/uterinecancer.html

"In the United States, cancer of the endometrium is the most common
cancer of the female reproductive organs. The American Cancer Society
expects there will be 40,100 new cases of cancer of the uterine body,
diagnosed in the United States during 2003. About 95% of these uterine
body cancers are endometrial cancer."

============================
DEALING WITH YOUR DIAGNOSIS
============================
http://tinyurl.com/ag3y

A comprehensive list of questions to ask your oncologist.

======================
STAGING
======================
http://www.cancerfacts.com/GeneralContent/Uterine/Gen_Diagnosis.asp?CB=11

Stage 1B = Invasion to less than one-half the myometrium (muscle wall)

======================
MECHANISMS OF MEGACE
======================
http://www.cancerwise.org/february_2002

"While the precise mechanism by which MEGACE produces its
antineoplastic effects against endometrial carcinoma is unknown at the
present time, inhibition of pituitary gonadotrophin production and
resultant decrease in estrogen secretion may be factors. There is
evidence to suggest a local effect as a result of the marked changes
brought about by the direct instillation of progestational agents into
the endometrial cavity."
DeSombre ER, Kuivanen PC: Progestin Modulation of Estrogen-Dependent
Marker Protein Synthesis in the Endometrium. Semin Oncol 1985;
12(Suppl 1):6.

=========================
DOSAGE AND ADMINISTRATION
=========================
http://www.ctclconsult.com/pdrdruginfo/html/10500600.htm

Breast Cancer: 160 mg/day (40 mg q.i.d.).

Endometrial Carcinoma: 40-320 mg/day in divided doses.

At least 2 months of continuous treatment is considered an adequate
period for determining the efficacy of MEGACE (megestrol acetate
tablets, USP).

========================
HORMONAL THERAPY
========================
http://www.meb.uni-bonn.de/cancer.gov/CDR0000062903.html

"The most common hormonal treatment has been progestational agents,
which produce good antitumor responses in up to 15% to 30% of
patients. These responses are associated with significant improvement
in survival. Progesterone and estrogen hormone receptors have been
identified in endometrial carcinoma tissues. Responses to hormones are
correlated with the presence and level of hormone receptors and the
degree of tumor differentiation. Standard progestational agents
include hydroxyprogesterone (Delalutin), medroxyprogesterone
(Provera), and megestrol (Megace)."

Semin Oncol 1994 Feb;21(1):100-6 
Advanced and recurrent endometrial carcinoma: hormonal therapy.
Lentz SS.  Section on Gynecologic Oncology, Wake Forest University,
Winston-Salem, NC 27517-1065.

***

Hormonal treatment of endometrial cancer: past, present and future.
Podczaski E, Mortel R.  Department of Obstetrics and Gynecology, Penn
State College of Medicine, The Milton S. Hershey Medical Center, 500
University Drive, Hershey, PA 17033-2390, USA.

"The concept that hormonal therapy may be useful in the treatment of
endometrial cancer antedated the pharmaceutical availability of
progestational compounds. By 1959, initial studies demonstrated the
ability of progestins to reverse endometrial hyperplasias. Thereafter,
progestins and other hormonal agents have been used in various roles
as treatment for endometrial cancers. This chapter reviews the use of
hormonal agents for the treatment of primary and metastatic/recurrent
endometrial cancer, as well as such treatment in an adjuvant setting.
Major problems in enhancing the efficacy of endocrine therapy of
cancers arising from hormonally responsive tissues are also
considered. The regulations of steroid-hormone receptor expression in
endometrial and breast cancers continues to be an active area of
research interest."


********************

===================
SPECIFIC QUESTIONS
===================
  
Can you find any scientific evidence why I should continue with
Megace?

Honestly, Ruby, I've spent quite a bit of time trying to substantiate
your continued use of Megace, but have found none.  As noted above the
standard dosing with Megace is for two months.  A couple of sites
visited added (or more), but I couldn't locate a source for an
extended course of treatment nor the reason for same.  That's not to
say there is none; only that I could not locate one.

********************

Q:  Is there another way to deal with the “suspicious” cytology
results besides Megace?
A:  Yes, most definitely!  Thankfully there are treatment approaches
which include surgical,  chemotherapeutic combinations, and other
treatment modalities.  As researchers, we don't have access to the
entire articles through PubMed, but hopefully you and your oncologist
can read and discuss the articles mentioned.

===============================
WHOLE-ABDOMINAL RADIATION (WAR)
===============================
http://tinyurl.com/af5f

Cancer J 2000 Nov-Dec;6(6):394-400 Related 

Whole-abdominal radiation in endometrial carcinoma: an analysis of
toxicity, patterns of recurrence, and survival.  Small W Jr, Mahadevan
A, Roland P, Vallow L, Zusag T, Fishman D, Massad S, Rademaker A,
Kalapurakal JA, Chang S, Lurain J.  Section of Radiation Oncology,
Robert H Lurie Cancer Center Northwestern University, Chicago,
Illinois, USA.

"Surgical staging results included 19% stage 1B, 4% stage IC, 8% stage
IIB, 37% stage IIIA, 26% stage IIIC, and 7% stage IVB. Two patients
had gross residual disease at the completion of surgery. Megestrol
acetate (Megace) was used as an adjuvant treatment in 37% of patients,
and no cases received initial chemotherapy. All patients received WAR
with a mean total dose and dose per fraction of 2620 and 143 cGy,
respectively. Twenty-two percent of patients received a para-aortic
boost. The mean total pelvic dose was 4956 cGy. Seventy percent of
patients received a vaginal cuff boost. Eight percent of patients had
grade 3 acute gastrointestinal morbidity, and 4% had grade 4 acute
gastrointestinal morbidity. No other grade 3 or greater acute or
long-term morbidity was noted. At last follow-up, seven (23%) patients
had experienced recurrence. The pattern of first recurrence was 0% in
the vaginal cuff, 3% other vaginal, 7% pelvic, 7% upper abdominal, 3%
lung, 7% bone, and 7% para-aortic lymph nodes. Ultimate recurrences
were similar. At last follow-up, 77% patients had no evidence of
disease, 13% were alive with disease, and 10% had died of disease.
CONCLUSIONS: Utilizing a conservatrive total whole-abdominal radiation
dose and limited para-aortic nodal boost resulted in very tolerable
treatments. The patterns of recurrence and survival in this early
report are encouraging."

=======================
MEGACE/TAMOXIFEN
=======================

http://www.medscape.com/viewarticle/417723_7  (Medscape articles by
registration)
Adenocarcinoma of the Endometrium: An Institutional Review
from Cancer Control: Journal of the Moffitt Cancer Center
Denis Cavanagh, MD, James V. Fiorica, MD, Mitchel S. Hoffman, MD, John
Durfee, MD, and Santo V. Nicosia, MD

"Local recurrences are usually at the vault of the vagina and/or in
the suburethral area. Localized recurrences in patients who have not
received previous radiotherapy may be treated with radiotherapy.
Metastases to bone can be treated with localized radiotherapy, which
is highly effective in relieving pain. For pulmonary metastases,
hormonal therapy with 80 to 320 mg/day of megestrol acetate (Megace)
or 20 to 40 mg/day of tamoxifen should be tried. A complete response
rate of approximately 20% has been reported with hormonal therapy.
Hormonal therapy is probably most effective when the tumor tissues
contain receptors. The value of 80 mg of megestrol acetate twice daily
for three weeks, alternating with 20 mg of tamoxifen twice daily for
three weeks, is being investigated in the Gynecologic Oncology Group
protocol 153. In cases where levels are low, chemotherapy should be
considered."

(...)

"The optimal treatment of early-stage endometrial carcinoma is still
not fully defined. Known and as yet unrecognized prognostic factors
must be sought by clinical and laboratory methods. New methods of
therapy for extensive disseminated or recurrent disease must be
carefully evaluated."

========================
HYSTERECTOMY
========================
http://www.nature.com/cgi-taf/DynaPage.taf?file=/bjc/journal/v88/n2/full/6600698a.html

(...)  "Our standard primary treatment for early-stage endometrial
carcinoma was surgery consisting of extrafascial total abdominal
simple hysterectomy, bilateral salpingo-oophorectomy and selective
pelvic and/or para-aortic lymphadenectomy. In cases in which
preoperative endometrial biopsy revealed histologic grade 1 tumour and
no macroscopic myometrial invasion was found during the operation,
lymphadenectomy was not performed. Para-aortic lymphadenectomy was
performed if para-aortic node metastasis was diagnosed by pathologic
sampling during the operation."

(...)

"We concluded that the presence of positive peritoneal cytology is not
an independent prognostic factor in patients with endometrial
carcinoma confined to the uterus, and adjuvant therapy does not appear
to be beneficial in these patients."

Impact of Hysterectomy:
http://www.cancer.org/docroot/CRI/content/CRI_2_4_4X_Surgery_63.asp?sitearea=

************************

Q:  Can I safely taper off Megace and not worry about a recurrence of
the cancer?
A:  From several studies, I would remain cautiously optimistic.

http://www.obgyn.net/newsrx/womens_health-Endometrial_Cancer-20010412-8.asp

"Use of estrogen replacement therapy (ERT), with or without
progestins, among women diagnosed with endometrial cancer does not
appear to increase their risk of recurring cancer or death, says new
research from the University of California-Irvine."

(...)

"Endometrial cancer, the fourth most common cancer in American women,
has an overall cure rate of over 70%."

Additional statistics from the SEER program:
http://surveillance.cancer.gov/statistics/types/survival.html

Q:  How have others who have taken Megace lost weight after
discontinuing the drug?
A:  I haven't found anything definitive with regard to weight loss
following Megace treatment.  I believe it's like any other weight
reduction regimen -- diet and exercise.  Also, with age comes a
decreased basal metabolism and unfortunately a person must redouble
their efforts with this additional hurdle.  Hopefully, with the
support groups I've listed below, you can log on and learn others'
secrets to weight loss.  However, I would encourage you to focus
primarily on returning to a vital state of health.

A few tips:
http://ourworld.compuserve.com/homepages/annemariegoossens/gencgi.htm
http://tinyurl.com/ag9y
"You can combat this by watching your dietary intake of carbohydrates
and fats, limiting your intake of simple sugars (through decreased
junk food and sodas), and increasing your activity level by walking
3-4 times a week, swimming, taking Tai Chi or yoga, or doing low
impact aerobics."


==================
ADDITIONAL LINKS
==================

Penn State Cancer Center Trials:
http://www.hmc.psu.edu/cancer/research

Support Information:
http://www.acor.org/support.html

Medline Resources:
http://www.nlm.nih.gov/medlineplus/ency/article/002166.htm

Cancer.gov:
http://www.nci.nih.gov/cancerinfo/pdq/treatment/endometrial/healthprofessional

Getting Well:
http://www.gettingwell.com/content/lifelong_health/chapters/fgac35.shtml

WebMD:
http://my.webmd.com/medical_information/condition_centers/uterine_cervical_cancer/default.htm

Research on the horizon:
http://tinyurl.com/agab

Complementary Therapy:
http://www.lef.org/protocols/prtcl-027.shtml

Additional studies of interest:

Berclaz G, Karamitopoulou E, Mazzucchelli L, Rohrbach V, Dreher E,
Ziemiecki A, Andres AC.
http://www.amedeo.com/medicine/gyn/EURJCAC.HTM

Ann Oncol 2003 Feb;14(2):220-6 
Activation of the receptor protein tyrosine kinase EphB4 in
endometrial hyperplasia and endometrial carcinoma.

Human cell line EN has a TP53 mutation: 
http://www.obgyn.net/newsheadlines/womens_health-Endometrial_Carcinoma-20030408-30.asp

Reed MJ, Hutton JD, Baxendale PM et al. The conversion of
androstenedione to oestrone and production of oestrone in women with
endometrial cancer. J Steroid Biochem 1979;11:905-11

H Sasano, S Sato, Kito : Effects of aromatase inhibitors on the
pathobiology of human breast endometrial and ovarian carcinoma.
Endocrine Related Cancer 6: 197 -204 , 1999.

Ruby, I trust this information is helpful to you and I wish you a very
speedy recovery.  Please let me know if I can assist you further.

Best regards,
V

Clarification of Answer by voila-ga on 27 Apr 2003 21:32 PDT
Approved labeling for Megace:
http://tinyurl.com/agnu

Clinical trials:
http://www.centerwatch.com/patient/studies/cat32.html

Vaginal brachytherapy
http://www.cancerpage.com/cancernews/cancernews3910.htm
Comments  
Subject: Re: Endometrial Cancer
From: voila-ga on 30 Apr 2003 12:15 PDT
 
Hello again, Ruby

I'm continuing to research your question as I would like to confirm
the protocol your oncologist is using.  I've also included some
additional links that I hope are useful to you.

In my previous postings, I failed to suggest that you might consider
obtaining a copy of at least your pathology report for your own
records.  Any physician participating in your care would be most
interested in including that information in your file.

Should I happen upon the protocol for Megace and its treatment
duration for stage 1B, I'll most certain post that information to you.

Cancer Group:
http://www.cancergroup.com/endo.html

Mets predictors:
http://tinyurl.com/aoaj

Physician login for cancer protocol:
http://www.cancerprotocol.com/index.html

Adenocarcinoma of the Endometrium: An Institutional Review
Denis Cavanagh, MD, James V. Fiorica, MD, Mitchel S. Hoffman, MD, John
Durfee, MD, and Santo V. Nicosia, MD  Cancer Control 6(4):354-360,
1999.  1999 H. Lee Moffitt Cancer Center and Research Institute, Inc
http://www.moffitt.usf.edu/pubs/ccj/v6n4/article4.htm

Aromatase in Endometrial Cancer 
http://edrv.endojournals.org/cgi/content/full/19/5/593

Women's Cancer Center:
http://www.wccenter.com/uterus.html

Info on positive cytology:
"Peritoneal Cytology is positive in 15% of patients with otherwise
stage I (Ref. Creasman, DiSaia Am J Obs. Gyn. 141:921,1981).
Recurrences developed in 35% of pts. with positive cytology, compared
with 10% with negative cytology. Most studies have shown higher
recurrences in patients with postive cytology, overall it’s associated
with only a 5% decrease in survival (Perez Ibid p.1204)."

Eifel Study:
"Eifel Study (Ref. Cancer 52:1026) looked at 256 cases with disease
limited to the uterine corpus. This Pennsylvania Hospital series
looked at recurrence risk for both patients with good and poor
prognostic findings at hysterectomy. Conclusions were that in patients
with stage I, grade I or II disease with no more than 1/3 myometrial
invasion, no further treatment was necessary since the prognosis of
these patients was good, with less than 5% risk of pelvic or vaginal
recurrence."
http://tinyurl.com/aodg

Full text articles:
http://www.gfmer.ch/Guidelines/Endometrial_cancer_guidelines.htm

Outreach links:
http://www.eyesontheprize.org/links/outreach.html

Regards,
V

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