palma dileo 1 ,
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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 Dileo 1 , - PowerPoint PPT PresentationTRANSCRIPT
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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
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Desmoid Fibromatosis (DF)
Abdominal
Extra-abdominal
Intra-abdominal
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Desmoid Fibromatosis (DF)
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DF: treatment options
Surgery
Radiation therapy
Medical therapy
Observation
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DF: medical options
Anti-estrogens (e.g., TAM)
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Chemotherapy • MTX + VBL/VNB
• doxorubicin-based chemotherapy
• …..
Interferons
Molecular therapy
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DF: a stepwise approach
Observation
Surgery and/or Radiotherapy
“Non aggressive” medical therapy
Molecular therapy
“Conventional” chemotherapy
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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
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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
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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
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Objectives and Endpoints
Objectives evaluate the antitumor activity of MTX + VBL/VNB or TAM
Endpoints• Primary
response rate
• Secondary progression-free survival
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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
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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
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MTX + VNB
After 26 cyclesBaseline
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TAM
Baseline After 1 year treatment
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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
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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
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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)
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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
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MTX+VBL/VNB:tolerability issues
Overall well tolerated
Mild hepatic toxicity (elevated transaminases) always regressed after dose decrease or treatment delay
Mild nausea
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TAM:tolerability issues
Overall well tolerated
Gynecomastia
Libido decrease
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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
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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
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Acknowledgments
We wish to thank
the patients and their families
the nurses, clinical staff, and radiologists, who have made this work possible
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Fondazione IRCCS Istituto Nazionale Tumori Milan, [email protected]