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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
Desmoid Fibromatosis (DF)
Abdominal
Extra-abdominal
Intra-abdominal
Desmoid Fibromatosis (DF)
DF: treatment options
Surgery
Radiation therapy
Medical therapy
Observation
DF: medical options
Anti-estrogens (e.g., TAM)
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Chemotherapy • MTX + VBL/VNB
• doxorubicin-based chemotherapy
• …..
Interferons
Molecular therapy
DF: a stepwise approach
Observation
Surgery and/or Radiotherapy
“Non aggressive” medical therapy
Molecular therapy
“Conventional” chemotherapy
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 NR NR 60 < 12
Reich et al. 1999 5 52 weeks 2 CR, 1 PR, 1 MR, 1 SD
60 7-76
Azzarelli et al. 2001 27 27 weeks 4 OR, 19 SD 17 6-96
Skapek et al. 2007 28 52 weeks 1 CR, 4 PR, 3 MR, 10 SD
40 NR
TAM:published evidence
Author # pts Duration of therapy
FAP Response Response duration (months)
Kinzbrunner et al. 1983 1 NR Yes PR NR
Rock et al. 1984 5 NR NR 2 SD, 3 PD NR
Procter et al. 1987 1 NR No SD 14
Thomas et al. 1990 1 NR No CR 12
Sportiello et al. 1991 1 NR No CR 27
Wilken et al. 1991 1 NR No PR 96
Mukherjee et al. 1995 1 NR NR PR 24
Chao et al. 2000 1 7 months No PR 72
Gwynne et al. 2005 1 NR No PR 168
Ohashi et al. 2006 1 NR No PR NR
Morris et al. 2007 1 NR No PR NR
Patient Disposition
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/m2 or 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
Objectives and Endpoints
Objectives evaluate the antitumor activity of MTX + VBL/VNB or TAM
Endpoints• Primary
response rate
• Secondary progression-free survival
Patient Characteristics (56 pts)
Sex Female 43 (76%)
Male 13 (24%)
Age Median (range) 29 (3-64) yrs
SyndromicSporadic 48 (86%)
FAP/Gardner 8* (14%)
Site
Abdominal (non mesenteric) 18 (32%)
Extra-abdominal 38 (68%)
* extra-abdominal locations
Tumor response
Best Response
No. of pts (%)MTX + VBL/VNB 11 (30%) PR
20 (55%) SD
4 (11%) PD
TAM 3 (15%) CR + PR
11 (55%) SD
6 (30%) PD
As of February 2008
MTX + VNB
After 26 cyclesBaseline
TAM
Baseline After 1 year treatment
MTX+VBL/VNB:duration of response
F 16 supraclavicular 52 PR 82
M 56 armpit 31 PR 62
F 49 arm 38 PR 209
F 23 abdominal wall 48 PR 35
M 34 paravertebral 40 PR 72
F 15 thigh 37 PR 43
M 26 supraclavicular 41 PR 124
F* 24 pelvis 52 PR 70
M 21 gluteal region & thigh 15 PR 57
F 61 scapular girdle 40 PR 88
F 29 supraclavicular 28 PR 84
Sex Age Primary Site # cycles Best response
Duration of Response(months)
Diagnosis during pregnancy
MTX+VBL/VNB:PFS
0 50 100 150 200 250
100
90
80
70
60
50
40
30
20
10
0
months
PF
S (
%)
Number at risk36 24 12 7 4 1
TAM:duration of response
F 58 neck 2 years CR 24
F 18 scapular girdle 2 years PR 20
M 45 thoracic wall 2 years PR 12
Sex Age Primary Site # cycles Best response
Duration of Response(months)
TAM:PFS
0 50 100 150 200
100
90
80
70
60
50
40
30
20
10
0
months
PF
S (
%)
Number at risk20 9 6 2 1
MTX+VBL/VNB:tolerability issues
Overall well tolerated
Mild hepatic toxicity (elevated transaminases) always regressed after dose decrease or treatment delay
Mild nausea
TAM:tolerability issues
Overall well tolerated
Gynecomastia
Libido decrease
Progression to TAMResponse MTX + VNB
Baseline PD to TAM MR to MTX + VNB
Of note, 5/6 pts progressed on TAM responded to MTX + VNB
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
Acknowledgments
We wish to thank
the patients and their families
the nurses, clinical staff, and radiologists, who have made this work possible
Fondazione IRCCS Istituto Nazionale Tumori Milan, Italypalma.dileo@istitutotumori.mi.it
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