State of the Art: Gestational Trophoblastic Lesions

1. State of the Art: Gestational Trophoblastic Lesions Treatment beyond single agents Barry Hancock (Sheffield, UK) International Gynecologic Society Meeting 2006

5. Which group of patients? • Risk (WHO score, Dutch classification) • Prognosis (Hammond) • Stage (Song, FIGO) • Choriocarcinoma risk (Japan) • Criteria for treatment

6. Two scenarios Single agent resistance ‘High’ risk disease

7. Single agent resistance Alternative single agent Combination chemotherapy (EMA-CO, MAC, EA etc)

8. 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

9. 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

10. What is the evidence base? • One randomized controlled trial • Lots of small-moderate sized series • One retrospective comparative study

11. 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!

12. 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%

13. 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)

14. Salvage treatment 20-60% success

15. Surgery

16. Toxicity EP-EMA CHAMOCA EMA-CO MAC EMA/MEA/FME

17. Toxicity • Multi-treated patients • Potential mortality whatever is chosen

18. Acute toxicity Alopecia +++++ Neutropenia ++++ Anemia +++ Nausea/vomiting ++ Stomatitis ++ Neutropenic sepsis ++ Thrombocytopenia +

19. Long-term toxicity • Increased second malignancy • Premature menopause • Unknown!

20. Staff Nurse Ellen Zitek in BBCs ‘Casualty’ Treated for ‘cancer’ after a molar pregnancy

23. 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

24. 459 (6%) High risk Low risk MTX 405 (88%) 54 (12%) MAE Resistant A 8 79 AE Sheffield Trophoblast Centre, UK1986-2005 Registration 8211 Persistent GTN

25. EA 79 Refractory 1 1 † CR 78 (99%) Methotrexate resistant GTN Median follow-up 8 years Late deaths 0 2nd malignancy 0 Further pregnancy >60%

26. Refractory 12 MEA 54 2 other TAH 5 5 CEC CR 42 (78%) + 7 4 1 2 1 4 † 49 (91%) alive and well Median follow-up 8.5 years Late deaths 0 2nd malignancy 0 Further pregnancy >60% High risk GTN

27. Cure rates in GTN Overall 98% cure

28. 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

32. CR MTX 22 6 (27%) Resistance 3 + 11 Other 4 AVC 12 20 Alive and well † 2 Methotrexate in high riskGTN (Sheffield, UK 1973-86) Median follow-up 24y Late deaths 0 2nd malignancies 0 AVC - dactinomycin, vincristine, cyclophosphmide