State of the Art: Gestational Trophoblastic Lesions
Treatment beyond single agents
Barry Hancock(Sheffield, UK)
International Gynecologic Society Meeting 2006
Which group of patients?
Risk (WHO score, Dutch classification)
Prognosis (Hammond)
Stage (Song, FIGO)
Choriocarcinoma risk (Japan)
Criteria for treatment
Two scenarios
Single agent resistance
‘High’ risk disease
Single agent resistance
Alternative single agent
Combination chemotherapy (EMA-CO, MAC, EA etc)
Single agent resistance
For ‘low’ risk non-metastatic disease single agent chemotherapy is 60-90% successful
Second line multi-agent therapy is virtually always (>95%) successful in dealing with single agent resistance
Benefits
Is intensive chemotherapy necessary for all high risk patients?
Higher CR
Less salvage treatment
Shorter treatment period
Risks
Over treatment
Higher financial costs
More toxicity
What is the evidence base?
One randomized controlled trial
Lots of small-moderate sized series
One retrospective comparative study
Primary treatment for high risk GTNMAC (MTX, dactinomycin, chlorambucil or cyclophosphamide)
EMA-CO (etoposide, MTX, dactinomycin, cyclophosphamide, vincristine)
EMA/MEA
CHAMOCA (cyclophosphamide, hydroxyurea, dactinomycin, MTX, vincristine, doxorubicin)
CHAMOMA (+ melphalan)
FME (FU, MTX, etoposide)
Previously single agent MTX!
Primary remission rates in high risk GTN
MAC 63-80%
CHAMOCA 82%
MAC vs CHAMOMA 73% vs 65%
EMA-CO >80%
EMA/MEA/FME 75-80%
Salvage treatment in high risk GTN
EMA-EP (EMA - etoposide, cisplatin)
BEP (bleomycin, etoposide, cisplatin)
CEC (cyclophosphamide, etoposide, cisplatin)
MISC (high dose chemotherapy, carboplatin/paclitaxel, paclitaxel/etoposide and paclitaxel/cisplatin doublet)
Salvage treatment
20-60% success
Surgery
Toxicity
EP-EMA
CHAMOCA
EMA-CO
MAC
EMA/MEA/FME
Toxicity
Multi-treated patients
Potential mortality whatever is chosen
Acute toxicityAlopecia +++++
Neutropenia ++++
Anemia +++
Nausea/vomiting ++
Stomatitis ++
Neutropenic sepsis ++
Thrombocytopenia +
Long-term toxicity
Increased second malignancy
Premature menopause
Unknown!
Staff Nurse Ellen Zitek in BBCs ‘Casualty’ Treated for ‘cancer’ after a molar pregnancy
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
Chemotherapy for High Risk GTN(Sheffield UK)
Day 1 MTX 100mg/m2 iv Folinic acid rescue
Day 8, 9, 10 Dactinomycin 500µg iv Etoposide 100mg/m2 iv
et seq 7 days
M/AE
Sheffield Trophoblast Centre, UK
1986-2005Registration 8211
459 (6%)Persistent GTN
Low risk High risk
54 (12%) MAE
79 8
405 (88%)MTX
Resistant
AEA
Methotrexate resistant GTN
CR 78 (99%)
EA 79 Refractory 1
1 †
Median follow-up 8 years
Late deaths 0
2nd malignancy 0Further pregnancy >60%
High risk GTNMEA 54
CR 42 (78%)
Refractory12 2 other
TAH 5 5 CEC
24 1+7
49 (91%) alive and well
Median follow-up 8.5 yearsLate deaths 0
Further pregnancy >60%2nd malignancy 0
1 4 †
Cure rates in GTN1st line Salvage
Low risk
(70-90%)75% 99%
High risk
(10-30%)75% 95%
Overall 98% cure
Conclusion The majority of patients are curable whatever the ‘risk’ or ‘stage’
It doesn’t seem to matter which regimen you choose as long as it works and you are familiar with it!
‘Specialist’ center skills may be more important than the actual therapy
But - occasional patients still die despite multiple chemotherapy and surgical interventions
Methotrexate in high riskGTN (Sheffield, UK 1973-86)
AVC - dactinomycin, vincristine, cyclophosphmide
Median follow-up 24y
22MTX
12 4Other
Resistance
AVC
6 (27%)CR
20 Alive and well3 + 11
2†Late deaths 0
2nd malignancies 0