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Welcome to Dr. Hamid Sanatinia's Virtual Headquarters
Gestational Trophoblastic Disease

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1. Classification & Risk Assessment
2. Chemotherapy
3. Link to Cancer Net (PDQ)
4. Overall treatment strategy based on risk assessment
5. Multimodaity Approach

GESTATIONAL TROPHOBLASTIC DISEASE
---Complete & partial molar pregnancy, invasive
mole, placental site trophoblastic tumor (PSTT), & choriocarcinoma.
---Highly curable, even with widespread metastases.
---Both complete & partial moles are characterized by an excessive amount of paternal chromosomes, which may induce trophoblastic hyperplasia.
---Complete moles usually have a 46,XX karyotype. All molar chromosomes are derived from paternal origin.
---Partial moles generally have a triploid karyotype.

CLINICAL CLASSIFICATION OF MALIGNANT GTD (NIH)
I. NON-METASTATIC GTD: no evidence of disease outside of uterus.
II. GOOD-PROGNOSIS METASTATIC GTD
Short duration (<4months)
Low hCG level (<40,000 mIU/ml serum b-hCG)
No brain or liver mets
No antecedent term pregnancy
No prior chemo
III. POOR-PROGNOSIS METASTATIC GTD
Long duration (>4months)
High pretreatment hCG levels (>40,00 mIU/ml)
Brain or liver mets
Antecedent term pregnancy
Prior chemotherapy

PATIENTS WHO ARE AT HIGH RISK FOR PERSISTENT GTD
1. age > 40
2. Preevacuation hCG>1,000,000 mIU
3. Uterine size >20 weeks
4. Thecaleutein csts
5. Prior mole

Should we use prophylactic chemotherapy?
Prophylactic methotrexate of high-risk patients-
With prophylaxis post-molar tumor incidence is 14%; without MTX, 47%. However, nearly 100% of patients with persistent GTD are successfully treated. Therefore, avoiding the toxic side effects of MTX.


NOTES ON GTD:
---HCG is a very reliable marker for this disease. However it is not reliable for PLACENTAL SITE TROPHOBLASTIC TUMORS (PSTs)
---A majority of patients who received single agent MTX or EMA/CO had subsequent successful live-birth pregnancies. (~83%)
---There is a small but significant risk of second tumors that can be induced by combination chemotherapy. These neoplasms include myeloid leukemia, colon cancer, & breast cancer.


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TREATMENT


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METHTREXATE 5-DAY REGIMEN

METHOTREXATE 0.4 mg/d IM X 5 days
Repeat Q 12-14 days


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METHOTREXATE + FOLINIC ACID

MTX 1 mg/Kg IM DAYS 1,3,5,7
FOLINIC ACID 0.11 mg/kg IM DAYS 2,4,6,8

REPEAT if hCG elevated or plateaued for 3 weeks


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WEEKLY METHOTREXATE

MTX 30 mg/m2 IM weekly


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DACTINOMYCIN 9-13 mg/kg IV X 5 days
Recycle q 14 days

DACTINOMYCIN 40 mg/kg IV Q14 days


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ETOPOSIDE

ETOPOSIDE 200 mg/m2 PO X 5 days
Recycle Q 14 days


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TREATMENT OF HIGH-RISK METASTATIC DISEASE

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EMA-CO REGIMEN (HIGH RISK MET)

Course A
DAY 1
ETOPOSIDE 100 mg/m2 IV over 30 min
METHOTREXATE 100 mg/m2 IV bolus
DAY 2
DACTINOYMCIN 500 ug IV bolus
ETOPOSIDE 100 mg/m2 IV over 30 min
DACTINOMYCIN 500 ug IV bolus
FOLINIC ACID 15 mg IM/PO Q 6 hours X 4 doses. Begin 12 hours after MTX

Course B
DAY 8
VINCRISTINE 1.0 mg/m2 IV bolus
CYCLOPHOSPHAMIDE 600 mg/m2 IV

DAY 15
RECYCLE COURSE A

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EP/EMA (for disease resistant to EMA/CO)

ETOPOSIDE 150 mg/m2 IV
CISPLATIN 75 mg/m2 IV with hydration
Alternate with EMA as described for EMA/CO except on day 2 patients only receive the folinic acid 15 mg BID X 48 hrs
Side effects include myelosuppression, renal impariment etc makes this regimen difficult to administer!

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MTX/DACTINOYCIN/CYCLOPHOSPHAMIDE REGIMEN

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CHAMOMOA (Bagshawe Regimen)

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Cancer Net (PDQ) web site for GTD

gtt.jpg

Overall treatment Strategy:

1. Non-metastatic
i- MTX
ii- MTX + Folinic Acid
iii- Weekly MTX
iv- Dactinomycin
v- Etoposide

2. Metastatic (Low-risk):
i- MTX
ii- Dactinomycin

3. Metastatic (High-risk):
COMBINATION CHEMOTHERAPY
i- EMA-CO
ii- MTX/DACTINOMYCIN/CYCLOPHOSPHAMIDE
iii-Bagshaw Regimen

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MULTIMODALITY TREATMENT:
1. Hysterectomy for patients who no longer desire fertility. Pro: Reduces the number of cycles of chemotherapy.
2. Whole brain radiation for brain mets. (3000 cGy).
3. Hepatic mets- Whole liver radiation (2000 cGy); Surgery; or embolization.
4. Surgery & resection of resistant foci in lung, bowel, or kidney.