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 Casali1 1Istituto Nazionale Tumori, Milan, Italy; 
2Campus Biomedico, Rome, Italy

2. Desmoid Fibromatosis (DF)
Abdominal
Extra-abdominal
Intra-abdominal 3

3. Desmoid Fibromatosis (DF)

4. DF: treatment options Surgery Radiation therapy Medical therapy
Observation 3

5. DF: medical options Anti-estrogens (e.g., TAM)
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Chemotherapy
MTX + VBL/VNB
doxorubicin-based chemotherapy
…..
Interferons
Molecular therapy 3

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

7. MTX + VBL/VNB: published evidence
Author
# pts
Duration of therapy
Response
RR (%)
FU (months)
Weiss et al. 1989 8 NR
2 CR, 4 PR, 1 MR 75
2-30
Skapek et al. 1998 10
52 weeks
3 CR, 2 PR, 3 SD, 2 PD 50
5-37
Weiss et al. 1999 13 60
< 12
Reich et al. 1999 5
2 CR, 1 PR, 1 MR, 1 SD
7-76
Azzarelli et al. 2001 27
27 weeks
4 OR, 19 SD 17
6-96
Skapek et al. 2007 28
1 CR, 4 PR, 3 MR, 10 SD 40

8. TAM: published evidence
Author
# pts
Duration of therapy
FAP
Response
Response duration (months)
Kinzbrunner et al. 1983 1 NR
Yes PR
Rock et al. 1984 5
2 SD, 3 PD
Procter et al. 1987 No SD 14
Thomas et al. 1990 CR 12
Sportiello et al. 1991 27
Wilken et al. 1991 96
Mukherjee et al. 1995 24
Chao et al. 2000
7 months 72
Gwynne et al. 2005
168
Ohashi et al. 2006
Morris et al. 2007

9. Patient Disposition Patients Treatment
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
30 mg/m2 + 6 mg/m2 or 50 mg + 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

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

11. Patient Characteristics (56 pts)
Sex
Female
43 (76%)
Male
13 (24%)
Age
Median (range)
29 (3-64) yrs
Syndromic
Sporadic
48 (86%)
FAP/Gardner
8* (14%)
Site
Abdominal (non mesenteric)
18 (32%)
Extra-abdominal
38 (68%)
* extra-abdominal locations

12. Tumor response Best Response No. of pts (%) As of February 2008
MTX + VBL/VNB
11 (30%) PR
20 (55%) SD
4 (11%) PD
TAM
3 (15%)
CR + PR
11 (55%)
6 (30%)

13. MTX + VNB
Baseline
After 26 cycles

14. TAM
Baseline
After 1 year treatment

15. MTX+VBL/VNB: duration of response
(months)
Sex
Age
Primary Site
# cycles
Best response F 16
supraclavicular 52 PR 82 M 56
armpit 31 62 49
arm 38
209 23
abdominal wall 48 35 34
paravertebral 40 72 15
thigh 37 43 26 41
124 F* 24
pelvis 70 21
gluteal region & thigh 57 61
scapular girdle 88 29 28 84
Diagnosis during pregnancy

16. MTX+VBL/VNB: PFS 50 100 150 200 250 90 80 70 60 40 30 20 10 months50
100
150
200
250 90 80 70 60 40 30 20 10
months
PFS (%)
Number at risk 36 24 12 7 4 1

17. TAM: duration of response
(months)
Sex
Age
Primary Site
# cycles
Best response F 58
neck
2 years CR 24 18
scapular girdle PR 20 M 45
thoracic wall 12

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

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
Baseline
PD to TAM
MR to MTX + VNB
Of note, 5/6 pts progressed on TAM responded to MTX + VNB

22. Conclusions
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

23. Acknowledgments We wish to thank the patients and their families
the nurses, clinical staff, and radiologists, who have made this work possible 16

24. Istituto Nazionale Tumori Milan, Italy
Fondazione IRCCS
Istituto Nazionale Tumori
Milan, Italy 3