Palma Dileo 1 ,

1. Activity of medical therapy (Methotrexate + Vinblastine/Vinorelbine or Tamoxifen) in Desmoid Fibromatosis (DF): retrospective analysis from a 76-patient single-institution series Palma Dileo1,  Claudio Piovesan1,  Marianna Silletta2,  Elisa Puma1,  Roberta Sanfilippo1,  Elisabetta Pennacchioli1,  Marco Fiore1,  Alessandro Gronchi1,  Paolo Giovanni Casali11Istituto Nazionale Tumori, Milan, Italy;  2Campus Biomedico, Rome, Italy

2. Abdominal Extra-abdominal Intra-abdominal Desmoid Fibromatosis (DF)

3. Desmoid Fibromatosis (DF)

4. Surgery Radiation therapy Medical therapy Observation DF: treatment options

5. Anti-estrogens (e.g., TAM) Nonsteroidal anti-inflammatory drugs (NSAIDs) Chemotherapy MTX + VBL/VNB doxorubicin-based chemotherapy ….. Interferons Molecular therapy DF: medical options

6. DF: a stepwise approach Observation Surgery and/or Radiotherapy “Non aggressive” medical therapy Molecular therapy “Conventional” chemotherapy

7. MTX + VBL/VNB:published evidence

8. TAM:published evidence

9. Patients 76 pts diagnosed with DF were analyzed (Dataset of the Istituto Nazionale Tumori, Milan, from 1977 to 2004) 56/76 received first line medical treatment as follows 36 MTX + VBL/VNB 20 TAM At the time of analysis, data were available from all pts treated Treatment MTX @ 30 mg/m2 + VBL @ 6 mg/m2or MTX @ 50 mg + VNB @ 30 mg/m2(every 10 days) MTX+VBL/VNB was administered for a median of 27 courses TAM from 10 to 60 mg daily up to 2 years Patient Disposition

10. Objectives evaluate the antitumor activity of MTX + VBL/VNB or TAM Endpoints Primary response rate Secondary progression-free survival Objectives and Endpoints

11. Patient Characteristics (56 pts) *extra-abdominal locations

12. Tumor response As of February 2008

13. MTX + VNB Baseline After 26 cycles

14. TAM After 1 year treatment Baseline

15. MTX+VBL/VNB:duration of response Duration of Response (months) Sex Primary Site # cycles Best response Age Diagnosis during pregnancy

16. 100 90 80 70 60 PFS (%) 50 40 30 20 10 0 0 50 100 150 200 250 months Number at risk 36 24 12 7 4 1 MTX+VBL/VNB:PFS

17. TAM:duration of response Duration of Response (months) Sex Age Primary Site # cycles Best response

18. 100 90 80 70 60 PFS (%) 50 40 30 20 10 0 0 50 100 150 200 months Number at risk 20 9 6 2 1 TAM:PFS

19. MTX+VBL/VNB:tolerability issues Overall well tolerated Mild hepatic toxicity (elevated transaminases)  always regressed after dose decrease or treatment delay Mild nausea

20. TAM:tolerability issues Overall well tolerated Gynecomastia Libido decrease

21. Progression to TAMResponse MTX + VNB PD to TAM MR to MTX + VNB Baseline Of note, 5/6 pts progressedon TAM responded to MTX + VNB

22. As shown by a few published studies, in this single-institution retrospective analysis MTX + VBL/VNB was associated with an interesting response, and prolonged SD, rate Likewise, as suggested by anecdotal-only published evidence, TAM was able to give tumor responses, occasionally major, as well as prolonged SDs Both medical therapies are of interest in a non-metastasizing disease, marked by a prolonged, variable natural history Possibly in sequence, both are useful options within a conservative stepwise medical treatment of this disease Conclusions

23. We wish to thank the patients and their families the nurses, clinical staff, and radiologists, who have made this work possible Acknowledgments

24. Fondazione IRCCS Istituto Nazionale Tumori Milan, Italy palma.dileo@istitutotumori.mi.it