State of the Art: Gestational Trophoblastic Lesions

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State of the Art Gestational Trophoblastic
Lesions

• Treatment beyond single agents
• Barry Hancock
• (Sheffield, UK)
• International Gynecologic Society Meeting 2006

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Which group of patients?

• Risk (WHO score, Dutch classification)
• Prognosis (Hammond)
• Stage (Song, FIGO)
• Choriocarcinoma risk (Japan)
• Criteria for treatment

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Two scenarios

• Single agent resistance
• High risk disease

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Single agent resistance

• Alternative single agent
• Combination chemotherapy
• (EMA-CO, MAC, EA etc)

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Single agent resistance

• For low risk non-metastatic disease single
  agent chemotherapy is 60-90 successful
• Second line multi-agent therapy is virtually
  always (gt95) successful in dealing with single
  agent resistance

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Is intensive chemotherapy necessary for all high
risk patients?
Benefits
Risks
? Higher CR
? Over treatment
? Less salvage treatment
? Higher financial costs
? Shorter treatment period
? More toxicity
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What is the evidence base?

• One randomized controlled trial
• Lots of small-moderate sized series
• One retrospective comparative study

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Primary treatment for high risk GTN

• MAC (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!
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Primary remission rates in high risk GTN

• MAC 63-80
• CHAMOCA 82
• MAC vs CHAMOMA 73 vs 65
• EMA-CO gt80
• EMA/MEA/FME 75-80

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Salvage treatment in high risk GTN

• EMA-EP (EMA - etoposide, cisplatin)
• BEP (bleomycin, etoposide, cisplatin)
• CEC (cyclophosphamide, etoposide, cisplatin)
• MISC (high dose chemotherapy, carboplatin/paclitax
  el,
• paclitaxel/etoposide and paclitaxel/cisplatin
  doublet)

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Salvage treatment

• 20-60 success

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Surgery
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Toxicity

• EP-EMA
• CHAMOCA
• EMA-CO
• MAC
• EMA/MEA/FME

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Toxicity

• Multi-treated patients
• Potential mortality whatever is chosen

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Acute toxicity

• Alopecia
• Neutropenia
• Anemia
• Nausea/vomiting
• Stomatitis
• Neutropenic sepsis
• Thrombocytopenia

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Long-term toxicity

• Increased second malignancy
• Premature menopause
• Unknown!

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• Staff Nurse Ellen Zitek in BBCs Casualty
• Treated for cancer after a molar pregnancy

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FIGO SCORING 0 1 2 4
Age lt 40 ? 40 - -
Antecedent pregnancy Mole Abortion Term -
Interval months from index pregnancy lt 4 4 - lt 7 7 - lt 13 ? 13
Pre-treatment serum hCG (IU/L) lt 103 103 - lt 104 104 - lt 105 ? 105
Largest tumour size (including uterus) cm lt 3 3 - lt 5 ? 5 -
Site of metastases Lung Spleen, kidney Gastro-intestinal Liver, brain
Number of metastases - 1-4 5-8 gt 8
Previous failed chemotherapy - - Single drug 2 or more drugs
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Chemotherapy for High Risk GTN(Sheffield UK)
M/AE

• Day 1 MTX 100mg/m2 iv Folinic acid
  rescue
• Day 8, 9, 10 Dactinomycin 500µg iv
• Etoposide 100mg/m2 iv
• et seq 7 days

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Sheffield Trophoblast Centre, UK1986-2005
Registration
8211
Persistent GTN
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Methotrexate resistant GTN

Median follow-up 8 years
Late deaths 0
2nd malignancy 0
Further pregnancy gt60
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High risk GTN
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Cure rates in GTN
1st line Salvage
Low risk (70-90) 75 99
High risk (10-30) 75 95
Overall 98 cure
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Conclusion

• The majority of patients are curable whatever
  the risk or stage
• It doesnt 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

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Methotrexate in high riskGTN (Sheffield, UK
1973-86)
Median follow-up 24y
Late deaths 0
2nd malignancies 0
AVC - dactinomycin, vincristine, cyclophosphmide