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Welcome to Dr. Hamid Sanatinia's Virtual Headquarters
Endometrial

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MDR

1. Hormonal Therapy
2. Single Agents
3. Combination Chemotherapy
4. Pathology
5. Risk Groups in endometrial cancer
6. Staging system
7. Management Recommendations


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HORMONAL THERAPY
In general response rate to hormonal therapy is in the vicinity of 20%. Agent of Choice is a progestin ie medroxyprogesterone 200 mg po QD. It is the first line systemic therapy for grade-1 or receptor positive tumors. It can also be used as salvage therapy after chemotherapy failure. In general, in grade 1 tumors, hormonal therapy is equivalent to chemotherapy. However, in grade2 or 3 disease, chemotherapy seems to be superior to hormonal therapy.


MEDROXYPROGESTERONE 100-200 mg PO, MEGESTROL ACETATE 160 mg PO,
TAMOXIFEN 20 mg po qd --2nd line or salvage RR 0-13%.

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CHEMOTHERAPY
(receptor negative or hormone refractory):

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Single Agents:
Doxorubicin RR=27%
Epirubicin RR=26%
Cisplatin RR=29%
Carboplatin RR=31%
Taxol RR=36%


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COMBINATION CHEMOTHERAPY:


DOXORUBICN + CISPLATIN (GOG-107)
DOXORUBICIN 60 mg/m2
CISPLATIN 50 mg/m2
Q 3wks X 8
This regimen produced a higher RR, CR, & PFI than single agent DOX. (i.e. RR 45% vs 27%) but median survival was not improved (8.7% vs 9.2).


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PACLITAXEL & CISPLATIN + GCSF
PACLITAXEL 175 mg/m(2) IV over a 3-h period, followed by
CISPLATIN 75mg/m(2) IV,
Followed with G-CSF.
Repeat Q3 weeks for a maximum of six courses.

REF: Gynecol Oncol 2000 Jul;78(1):52-7 16 patients (67%; 95% confidence interval, 45-84%) achieved OR, including 7 CRs and 9 PRs. The median duration of response was 7 months, and the median TTP & survival for all patients were 8.4 & 17.6 months, respectively.

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JMF-M REGIMEN:
CARBOPLATIN (300 mg/m2),
METHOTREXATE (30 mg/m2),&
5FU (500 mg/m2)
Given on day 1, in a 3-weekly schedule, in combination with
MEDROXYPROGESTERONE ACETATE (MPA) 300 mg PO QD., until progression

REF: Oncology 1999 Apr;56(3):198-201. REPORT: OR 17/23 patients (74%, 95% confidence interval = 52-90%), with 2 long-lasting CRs (9%). The median response duration was 10+ months (3-45+). The median survival was 16+ months (2-45+). SIDE EFFECTS: Myelosuppression (less than 14% leukopenia, anemia and thrombocytopenia). The MPA-related side effects were: weight gain (22%), hypertension (17%) and thromboplebitis (17%).

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DOXORUBICIN + PACLITXEL GOG-163
results pending!

DOXORUBICIN + CISPLATIN + PACLITXEL GOG-177
results pending!

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CARBOPLATIN+TAXOL

Carboplatin AUC=5 to 7)
Paclitaxel 175 mg/m2 for 3 hours
Q 4-weeks:

REF= JCO 19, Issue 20 (October), 2001: 4048-4053
N=60
group 1 (n = 21), primarily advanced, nonpapillary serous cancers; RR78% (95% CI, 51%-100%);
group 2 (n = 20), the same as group 1 but with papillary serous cancers; RR60% (95% CI, 35%-85%),
group 3 (n = 18), recurrent, nonpapillary serous cancers; RR 56% (95% CI, 34% to 78%)
group 4 (n = 4), recurrent, papillary serous cancers;RR 50%
Involved-field irradiation was used in groups 1 & 2 for those with radioencompassable disease.
19 patients (90%) in group 1 were irradiated, and the median failure-free survival time for all 21 patients was 23 months, with a 62% 3-year overall survival rate. 11 patients (55%) in group 2 were irradiated, & the median FFS for all 18 patients = 18 months, with a 39% 3-year OS. The median FFS in the patients in group 3 = 6 months, with a 15-month median OS. Toxicity was manageable, reversible, and predominantly hematologic. 2 patients developed neutropenic fever, & 3 patients, including these two, were hospitalized for complications.

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Pathology
1. Endometroid Adenocarcinoma (well-diff to poorly diff)
2. Adenocanthoma - adenocarcinoma with bening squamous differentiation. Good prognosis.
3. Adenosquamous carcinoma - The squamous component resembles squamous carcinoma. Worse prognsis.
4. Serous carcinoma - Very aggressive.
5. Clear-cell carcinoma - Poor prognosis. Early intraperitoneal spead.
6. Secretory adenocarcinoma - resembles secretory endometrium. Low grade, good prognosis.


Endometrial Cancer Risk Stratification:

LOCOREGIONAL DISEASE
Low-Risk: Stage IA grades 1-2
Intermediate-Risk: All other stage I; Stage II, Stage IIIA
High-Risk: All other stage III & Stage IVA

DISSEMINATED DISEASE
Stage IVB or recurrent disease
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RISK GROUPS IN ERALY ENDOMETRIAL CARCINOMA

HIGH RISK (1 or more factors present):
Grade 3 lesion
Grade 1 or 2 lesion + deep myometrial invasion
Positive pelvic or para-aortic LN
Positive peritoneal cytology
Stromal invasion of the cervix
Extrauterine spread

LOW RISK (all factors present):
Grade 1 0r 2 lesion without deep myometrial invasion
Negative peritoneal cytology
No stromal invasion of the cervix
No extrauterine spread
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Staging System (also need to include tumor grade):
0 = CIS
I = Confined to the UTERUS. [SURVIVAL ~90%]
II= Involves the corpus & cervix but does not extend outside uterus. [SURVIVAL ~60%]
III= Extends outside uterus but not outside true pelvis. [SURVIVAL ~40%]
IV= Extends outside true pelvis or involves the bladder or rectal mucosa. [SURVIVAL ~<10%]

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Management Recommendations for Endometrial Carcinoma
---LIMITED DISEASE---
LOW RISK- TAH+BSO
HIGH RISK- TAH+BSO + XRT
---ADVANCED OR RECURRENT DISEASE---
LOCOREGIONAL
If confined to the uterus, ovaries, & fallopian tubes then perform radical hysterectomy & pelvic node dissection followed by pelvic XRT. Otherwise, XRT!
DISSEMINATED
Use progestins or tamoxifen for well-differeniated or receptor positive tumors. Otherwise, chemotherapy is recommended
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