pmh clinical practice guidelines template practice guidelines ... molar pregnancy is typically...

PRINCESS MARGARET CANCER CENTRE

CLINICAL PRACTICE GUIDELINES

GYNECOLOGIC CANCER

GESTATIONAL TROPHOBLASTIC DISEASE

Last Revision Date – July 2015 2

Site Group: Gynecology – Gestational Trophoblastic Cancer

Author: Dr. Stephane Laframboise

1. INTRODUCTION 3

2. PREVENTION 3

3. SCREENING AND EARLY DETECTION 3

4. DIAGNOSIS 3

5. PATHOLOGY 4

6. MANAGEMENT 5

6.1 MANAGEMENT ALGORITHMS 5 6.2 MOLAR PREGNANCY 8

6.3 SURGERY 8

6.4 CHEMOTHERAPY 8 6.5 ONCOLOGY NURSING PRACTICE 14

7. SUPPORTIVE CARE 14

7.1 PATIENT EDUCATION 14 7.2 PSYCHOSOCIAL CARE 14 7.3 SYMPTOM MANAGEMENT 14 7.4 CLINICAL NUTRITION 14 7.5 PALLIATIVE CARE 14

8. FOLLOW-UP CARE 15


1. Introduction

Gestational Trophoblastic Disease (GTD) represents a spectrum of rare clinical and

pathologic syndromes related to abnormal placental growth and development. GTD

includes both benign and malignant forms of diseases of trophoblast, whereas gestational

trophoblastic neoplasia (GTN) refers to those entities that potentially behave in a

malignant manner and are thus treated as such. GTN may arrive de novo post an

apparently otherwise normal pregnancy (or rarely ectopic or aborted pregnancy) or more

typically after the occurrence of a non-resolving molar gestation. Based on evidence

from multiple jurisdictions from around the world, it is recommended that these patients

be managed in a centralized manner by experienced clinicians/centres to achieve optimal

patient outcomes.

2. Prevention

Not applicable at this time.

3. Screening and Early Detection

There are no currently no screening practices in place for GTN. Early detection relies on

clinical case identification including appropriate follow-up of patients found to have a

molar gestation to ensure complete resolution. There is a small population at women at

risk for GTD based on prior and/or family history however there is no specific program

available for their management at this time.

4. Diagnosis

Molar pregnancy is typically detected in early pregnancy as the result of ultrasound and

hCG measurements performed during early pregnancy care. GTN is typically diagnosed

during surveillance monitoring of hCG post evaculation of a molar pregnancy, although it

might be detected at a remote time via either an elevated hCG in the setting of clinical

findings on exam or radiology, or after biopsy of a mass lesion.

For those patients diagnosed with a form of GTN, the staging workup consists of :

History/physical exam

Chest X-Ray or CT thorax

Bloodwork (CBC, LFTs, Cr, hCG tumour marker)

Pelvic US

CT abdomen/pelvis

CT/MRI brain if symptoms or CXR positive


FIGO Staging of GTN

Stage 1 Disease confined to the uterus

Stage 2 GTN extends outside the uterus but is limited to the genital structures (adnexa, vagina, broad ligament)

Stage 3 GTN extends to the lungs with or without genital tract involvement

Stage 4 All other metastatic sites

WHO Prognostic score for GTN

FIGO Scoring 0 1 2 4

Age <40 ≥40

Antecedent Pregnancy Mole Abortion Term

Interval months from index pregnancy

<4 4 - <7 7 - <13 ≥13

Pre-treatment serum hCG (IU/L)

<10³ 10³ - <10⁴ 10⁴ - <10⁵ ≥10⁵

Largest tumour size (including Uterus) cm

<3 3 - <5 ≥5

Site of metastases Lung Spleen, Kidney

Gastro-intestinal Liver, Brain

Number of metastases 1 - 4 5 - 8 >8

Previous failed chemotherapy

Single drug 2 or more drugs

5. Pathology

• Expert pathology review of material from prior suction D&C for cases of hydatidiform

molar pregnancy

• Expert pathology review of biopsy material to confirm diagnosis of choriocarcinoma,

PSTT, or ETT

• Rarely microgenetic analysis is beneficial to explore the potential for underlying genetic

mutation responsible for recurrent GTN syndromes


6. Management

6.1 Management Algorithms

6.1.1 Molar Pregnancy


6.1.2 GTN (persistent mole post D&C, choriocarcinoma, PSTT)


6.1.3 Recurrence/Persistence


6.2 Molar Pregnancy

Surgery for Molar Pregnancy

suction D&C

Follow up

serial hCG follow-up weekly until negative

contraception

follow-up monthly hCG for 6 months

If meets criteria for persistence (plateau, rise, or persistence), proceed to GTN treatment

6.3 Initial Surgery for GTN

If patient with stage I desires fertility, repeat suction d&c can be considered

If patient with stage I does NOT desire fertility, hysterectomy may be considered.

Consider surgery for PSTT

6.4 Initial Chemotherapy for GTN

LOW RISK (WHO score <7)

Single agent chemotherapy (ACT-D or MTX)

ACT-D regimen: 1.25mg/m2 IV q2 wk until 2 cycles past negative

MTX regimen: 300mg/m2 IV q1 wk until 2 cycles past negative

HIGH RISK (WHO score 7-11)

Multiagent chemotherapy (EMA-CO)

EMA-CO regimen: Day 1: EMA (inpatient), Day 8: CO (outpatient)

ULTRA-HIGH RISK (WHO score >12 or PSTT)

Multiagent chemotherapy (EP-EMA)

EP-EMA regimen: Day 1: EP (outpatient), Day 8: EMA (inpatient)

Other regimens potentially for persistence include:

BEP, ICE, TE/TP


WEEKLY METHOTREXATE FOR GTN

DAY DRUG DOSE UNIT MAX RTE VOL FLUID TYPE FRQ DUR QTY REFILL

--- ---- ---- ---- --- --- --- ----- ---- --- --- --- ------

1 SODIUM BICARBONATE 50 mEq/FIX IV 1000ML 2/3 O ONCE MIX IN

2/3 & 1/3 FLUID. INFUSE IV OVER 2 HOURS PRE-METHOTREXATE.

1 ONDANSETRON 8 mg/FIX PO O ONCE PRN

GIVE ONCE IF PT DID NOT BRING OWN SUPPLY. TAKE FROM PYXIS

1 DEXAMETHASONE 8 mg/FIX PO O ONCE PRN GIVE

ONCE IF PT DID NOT BRING OWN SUPPLY. PT SHOULD TAKE WITH FOOD. TAKE FROM PYXIS

1 METHOTREXATE SODIUM 300 mg/M2 IV 1000ML NS O ONCE INFUSE

IV OVER 1-2 HOURS

*REMIND PATIENT TO START LEUCOVORIN 24 HOURS AFTER THE START OF METHOTREXATE INFUSION*

2 LEUCOVORIN CALCIUM 15 mg/FIX PO H Q6H

TAKE 15 MG EVERY 6 HOURS FOR 4 DOSES, STARTING 24 HOURS AFTER STARTING METHOTREXATE

*REMIND PATIENT TO START LEUCOVORIN 24 HOURS AFTER THE START OF METHOTREXATE INFUSION*

POST REGIMEN ============


1 PROCHLORPERAZINE MALEATE 10 mg/FIX PO H Q6H PRN 10 Days

EVERY 6 HOURS AS NEEDED FOR NAUSEA OR VOMITING.

ACTINOMYCIN D Q 2 WEEKLY for GTN

Regimen: GY-DACTINO DACTINOMYCIN

Repeat: 14 Days

PRE REGIMEN ==========



--- ---- ---- ---- --- --- --- ----- ---- --- --- --- ------

1. ONDANSETRON 2 mg/FIX PO H ONCE 1 Days 2

TAKE AT LEAST 1 HOUR PRIOR TO CHEMO ON TREATMENT DAY 1

1 DEXAMETHASONE 20 mg/FIX PO H ONCE 1 Days

TAKE WITH FOOD AT LEAST 1 HOUR PRIOR TO CHEMO ON TREATMENT DAY 1

REGIMEN

1 DEXAMETHASONE 20 mg/FIX PO O ONCE PRN

GIVE ONCE IF PT DID NOT BRING OWN SUPPLY. PT SHOULD TAKE WITH FOOD. TAKE FROM PYXIS

1 DACTINOMYCIN 1.25 mg/M2 2mg PIV O ONCE

IV PUSH

POST REGIMEN

============


--- ---- ---- ---- --- --- --- ----- ---- --- --- --- ------

2 ONDANSETRON 8 mg/FIX PO H BID 1 Days

THREE A DAY FOR 1 DAY STARTING THE DAY AFTER CHEMOTHERAPY (DAY 2).

2 DEXAMETHASONE 4 mg/FIX PO H BID 2 Days

TWICE A DAY WITH FOOD FOR 2 DAYS STARTING THE DAY AFTER CHEMOTHERAPY (ON DAYS 2-3).

1 PROCHLORPERAZINE MALEATE 10 mg/FIX PO H Q6H PRN 10 Days 30

EVERY 6 HOURS AS NEEDED FOR NAUSEA OR VOMITING


EMACO for GTN

PRE REGIMEN

========== DAY DRUG DOSE UNIT MAX RTE VOL FLUID TYPE FRQ DUR QTY REFILL

--- ---- ---- ---- --- --- --- ----- ---- --- --- --- ------

1 ONDANSETRON 8 mg/FIX PO H QD 3 Days 6

TAKE AT LEAST 1 HOUR PRIOR TO CHEMO ON TREATMENT DAYS 1, 2 AND 8

--------------------------------------------

1 DEXAMETHASONE 0 mg/FIX PO H QD 3 Days 12

TAKE 20 MG WITH FOOD AT LEAST 1 HOUR PRIOR TO CHEMO ON TREATMENT DAYS 1 AND 2. TAKE 8 MG WITH FOOD AT LEAST 1 HOUR PRIOR

TO CHEMO ON TREATMENT DAY 8

POST REGIMEN ============


--- ---- ---- ---- --- --- --- ----- ---- --- --- --- ------

1 PROCHLORPERAZINE MALEATE 10 mg/FIX PO H Q6H PRN 10 Days 30

EVERY 6 HOURS AS NEEDED FOR NAUSEA OR VOMITING

2 ONDANSETRON 8 mg/FIX PO H BID 2 Days

TWICE or THREE A DAY FOR 2 DAYS ON DAYS 2 AND 3.

.

2 DEXAMETHASONE 4 mg/FIX PO H BID 2 Days

TWICE A DAY WITH FOOD FOR 2 DAYS ON DAYS 2 AND 3.

REGIMEN EMACO for GTN


--- ---- ---- ---- --- --- --- ----- ---- --- --- --- ------


GIVE ONCE IF PT DID NOT BRING OWN SUPPLY. TAKE FROM PYXIS



1 DACTINOMYCIN 0.5 mg/FIX PIV O ONCE

IV PUSH


1 ETOPOSIDE 100 mg/M2 IV 500ML NS O ONCE

INFUSE IV OVER 1 HOUR.

*USE NON-PVC EXCEL BAG & LOW-ADSOPTION TUBING WITH 0.22 MICRON IN-LINE FILTER*

1 SODIUM BICARBONATE 50 mEq/FIX IV 1000ML 2/3 O ONCE

INFUSE IV OVER 2 HOURS PRE-METHOTREXATE.

1 METHOTREXATE SODIUM 100 mg/M2 IV 100ML NS O ONCE

INFUSE IV OVER 30 MINUTES.

1 METHOTREXATE SODIUM 200 mg/M2 IV 500ML NS O ONCE

INFUSE IV OVER 6 HOURS

1 DIPHENHYDRAMINE HCL 50 mg/FIX IV 50ML NS O Q4H PRN

ADMINISTER IV OVER 15-30 MINUTES EVERY 4 HOURS AS NEEDED.

MAXIMUM DAILY DOSE OF DIPHENHYDRAMINE ALLOWED IN CHEMO DAYCARE FOR ALLERGIC REACTIONS IS 200 MG.


GIVE ONCE IF PT DID NOT BRING OWN SUPPLY



2 ETOPOSIDE 100 mg/M2 IV 500ML NS O ONCE

INFUSE IV OVER 1 HOUR.

*USE NON-PVC EXCEL BAG & LOW-ADSOPTION TUBING WITH 0.22 MICRON IN-LINE FILTER*

2 DACTINOMYCIN 0.5 mg/FIX PIV O ONCE

IV PUSH

2 LEUCOVORIN CALCIUM 15 mg/FIX PO H Q6H 1 Days

EVERY 6 HOURS FOR 4 DOSES ONLY, STARTING 24 HOURS AFTER START OF METHOTREXATE INFUSION

START 24HR AFTER COMMENCING METHOTREXATE

2 DIPHENHYDRAMINE HCL 50 mg/FIX IV 50ML NS O Q4H PRN

ADMINISTER IV OVER 15-30 MINUTES EVERY 4 HOURS AS NEEDED.

MAXIMUM DAILY DOSE OF DIPHENHYDRAMINE ALLOWED IN CHEMO DAYCARE FOR ALLERGIC REACTIONS IS 200 MG.



GIVE ONCE IF PT DID NOT BRING OWN SUPPLY



8 VINCRISTINE SULFATE 1 mg/M2 2mg IV 50ML NS O ONCE

**FOR INTRAVENOUS USE ONLY** INFUSE AS A WIDE-OPEN IV BY GRAVITY.

RN MUST REMAIN AT BEDSIDE TO OBSERVE THE IV SITE FOR EXTRAVASATION DURING THE ENTIRE INFUSION.

DO NOT USE PUMP.

DURATION OF INFUSION MAY VARY DEPENDING ON PATIENT'S VENOUS CONDITION.

8 CYCLOPHOSPHAMIDE 600 mg/M2 IV 250ML NS O ONCE

NFUSE IV OVER 30 MINUTES

14

Last Revision Date – July 2015

6.5 Oncology Nursing

Refer to general oncology nursing practices

7. Supportive Care

7.1 Patient Education

Refer to general patient education practices

7.2 Psychosocial Care

Refer to general psychosocial oncology care guidelines

7.3 Symptom Management

Refer to general symptom management care guidelines

7.4 Clinical Nutrition

Refer to general clinical nutrition care guidelines

7.5 Palliative Care

Refer to general oncology palliative care guidelines

http://www.uhn.ca/PrincessMargaret/Health_Professionals/Programs_Departments/Pages/clinical_practice_guidelines.aspx






15


8. Follow-up Care

All patients require hCG monitoring during a post-treatment to ensure durable treatment

effect:

Molar gestation: 6 months

Low-risk GTN: 6-12 months

High-risk GTN: 12-24 months

β-hCG monitoring involves hCG tumour marker measurement and regression curve

plotting throughout and post completion of treatment (initially weekly until negative x 1

month, then monthly for duration as noted above)

Patients are also generally seen every 3 months during monitoring period for symptom

review, ± Physical Exam - Abdomen / Pelvis, and confirmation of ongoing contraception

and toxicity concerns. Thereafter follow-up is generally tailored to needs and risk of

individual patients.

Recurrence

Upon detection of treatment failure, patients should be restaged and WHO score

recalculated as noted above.

Treatment options will depend on the stage of disease, patient’s fertility wishes, and

WHO score.

a. Surgery for Recurrent GTN

If patient with stage I does NOT desire fertility, hysterectomy may be considered, should

be primary therapy for PSTT in this situation

If patient with oligometastasis are surgical candidates, surgery may be considered (ie

lungs, liver, hysterectomy)

b. Recurrent Chemotherapy for GTN

LOW RISK (WHO score <7)

Alternate single agent chemotherapy (ACT-D or MTX)

ACT-D regimen: 1.25mg/m2 IV q2 wk until 2 cycles past negative

MTX regimen: 300mg/m2 IV q1 wk until 2 cycles past negative

HIGH RISK (WHO score 7-11)

Multiagent chemotherapy (EMA-CO)

EMA-CO regimen: Day 1: EMA (inpatient), Day 8: CO (outpatient)

16


ULTRA-HIGH RISK (WHO score >12 or PSTT)

Multiagent chemotherapy (EP-EMA)

EP-EMA regimen: Day 1: EP (outpatient), Day 8: EMA (inpatient)

Other regimens potentially for persistence include:

BEP, ICE, TE/TP

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