PMID- 24703573
OWN - NLM
STAT- MEDLINE
DCOM- 20140703
LR  - 20220408
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Linking)
VI  - 50
IP  - 9
DP  - 2014 Jun
TI  - Activity of sunitinib in extraskeletal myxoid chondrosarcoma.
PG  - 1657-64
LID - S0959-8049(14)00256-1 [pii]
LID - 10.1016/j.ejca.2014.03.013 [doi]
AB  - BACKGROUND: Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue 
      sarcoma, marked by NR4A3 rearrangement. Herein we report on the activity of 
      sunitinib in a series of 10 patients, strengthening what initially observed in 
      two cases. PATIENTS AND METHODS: From July 2011, 10 patients with progressive 
      metastatic translocated EMC have been consecutively treated with sunitinib 
      37.5mg/day, on a named-use basis. In an attempt to interpret the activity of 
      sunitinib in EMC, genotype/phenotype correlations were carried out by 
      fluorescence in situ hybridization (FISH) analyses. Moreover, transcriptome, 
      immunohistochemical and biochemical analyses of a limited set of samples were 
      performed focusing on some putative targets of sunitinib. RESULTS: Eight of 10 
      patients are still on therapy. Six patients had a Response Evaluation Criteria in 
      Solid Tumours (RECIST) partial response (PR), two were stable, two progressed. 
      Positron emission tomography (PET) was consistent in 6/6 evaluable cases. One 
      patient underwent surgery after sunitinib, with evidence of a pathologic 
      response. At a median follow-up of 8.5 months (range 2-28), no secondary 
      resistance was detected. Median progression free survival (PFS) has not been 
      reached. Interestingly, all responsive cases turned out to express the typical 
      EWSR1-NR4A3 fusion, while refractory cases carried the alternative TAF15-NR4A3 
      fusion. Among putative sunitinib targets, only RET was expressed and activated in 
      analysed samples. CONCLUSIONS: This report confirms the therapeutic activity of 
      sunitinib in EMC. Genotype/phenotype analyses support a correlation between 
      response and EWSR1-NR4A3 fusion. Involvement of RET deserves further 
      investigation.
CI  - Copyright (c) 2014 Elsevier Ltd. All rights reserved.
FAU - Stacchiotti, S
AU  - Stacchiotti S
AD  - Adult Mesenchymal Tumor Medical Oncology Unit, Cancer Medicine Department, 
      Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. Electronic address: 
      silvia.stacchiotti@istitutotumori.mi.it.
FAU - Pantaleo, M A
AU  - Pantaleo MA
AD  - Dipartimento di Medicina Sperimentale, Specialistica e Diagnostica, Universita di 
      Bologna, Bologna, Italy.
FAU - Astolfi, A
AU  - Astolfi A
AD  - Centro Interdipartimentale di Ricerche sul Cancro "G. Prodi", Universita di 
      Bologna, Bologna, Italy.
FAU - Dagrada, G P
AU  - Dagrada GP
AD  - Experimental Molecular Pathology Unit, Department of Pathology, Fondazione IRCCS 
      Istituto Nazionale Tumori, Milan, Italy.
FAU - Negri, T
AU  - Negri T
AD  - Experimental Molecular Pathology Unit, Department of Pathology, Fondazione IRCCS 
      Istituto Nazionale Tumori, Milan, Italy.
FAU - Dei Tos, A P
AU  - Dei Tos AP
AD  - Department of Anatomic Pathology, General Hospital of Treviso, Treviso, Italy.
FAU - Indio, V
AU  - Indio V
AD  - Centro Interdipartimentale di Ricerche sul Cancro "G. Prodi", Universita di 
      Bologna, Bologna, Italy.
FAU - Morosi, C
AU  - Morosi C
AD  - Department of Radiology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, 
      Italy.
FAU - Gronchi, A
AU  - Gronchi A
AD  - Department of Surgery, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
FAU - Colombo, C
AU  - Colombo C
AD  - Department of Surgery, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
FAU - Conca, E
AU  - Conca E
AD  - Experimental Molecular Pathology Unit, Department of Pathology, Fondazione IRCCS 
      Istituto Nazionale Tumori, Milan, Italy.
FAU - Toffolatti, L
AU  - Toffolatti L
AD  - Department of Anatomic Pathology, General Hospital of Treviso, Treviso, Italy.
FAU - Tazzari, M
AU  - Tazzari M
AD  - Unit of Immunotherapy of Human Tumors, Fondazione IRCCS Istituto Nazionale 
      Tumori, Milan, Italy.
FAU - Crippa, F
AU  - Crippa F
AD  - Department of Nuclear Medicine, Fondazione IRCCS Istituto Nazionale Tumori, 
      Milan, Italy.
FAU - Maestro, R
AU  - Maestro R
AD  - Unit of Experimental Oncology 1, CRO Aviano National Cancer Institute, Aviano, 
      Italy.
FAU - Pilotti, S
AU  - Pilotti S
AD  - Experimental Molecular Pathology Unit, Department of Pathology, Fondazione IRCCS 
      Istituto Nazionale Tumori, Milan, Italy.
FAU - Casali, P G
AU  - Casali PG
AD  - Adult Mesenchymal Tumor Medical Oncology Unit, Cancer Medicine Department, 
      Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140402
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Calmodulin-Binding Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (EWSR1 protein, human)
RN  - 0 (Indoles)
RN  - 0 (NR4A3 protein, human)
RN  - 0 (Pyrroles)
RN  - 0 (RNA-Binding Protein EWS)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Receptors, Steroid)
RN  - 0 (Receptors, Thyroid Hormone)
RN  - 0 (TAF15 protein, human)
RN  - 0 (TATA-Binding Protein Associated Factors)
RN  - EC 2.7.10.1 (FLT3 protein, human)
RN  - EC 2.7.10.1 (KDR protein, human)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-ret)
RN  - EC 2.7.10.1 (RET protein, human)
RN  - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor beta)
RN  - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2)
RN  - EC 2.7.10.1 (fms-Like Tyrosine Kinase 3)
RN  - V99T50803M (Sunitinib)
RN  - Chondrosarcoma, Extraskeletal Myxoid
SB  - IM
MH  - Adult
MH  - Aged
MH  - Angiogenesis Inhibitors/*therapeutic use
MH  - Antineoplastic Agents/*therapeutic use
MH  - *Bone Neoplasms
MH  - Calmodulin-Binding Proteins/genetics
MH  - Chondrosarcoma/*drug therapy/genetics/secondary
MH  - DNA-Binding Proteins/genetics
MH  - Drug Resistance, Neoplasm/genetics
MH  - Female
MH  - Gene Rearrangement/genetics
MH  - Genotype
MH  - Humans
MH  - Indoles/*therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Neoplasms, Connective and Soft Tissue/*drug therapy/genetics/secondary
MH  - Phenotype
MH  - Proto-Oncogene Proteins c-kit/drug effects
MH  - Proto-Oncogene Proteins c-ret/drug effects
MH  - Pyrroles/*therapeutic use
MH  - RNA-Binding Protein EWS
MH  - RNA-Binding Proteins/genetics
MH  - Receptor, Platelet-Derived Growth Factor beta/drug effects
MH  - Receptors, Steroid/genetics
MH  - Receptors, Thyroid Hormone/genetics
MH  - Sunitinib
MH  - TATA-Binding Protein Associated Factors/genetics
MH  - Treatment Outcome
MH  - Vascular Endothelial Growth Factor Receptor-2/drug effects
MH  - fms-Like Tyrosine Kinase 3/drug effects
OTO - NOTNLM
OT  - Antiangiogenic
OT  - Chemotherapy
OT  - Chondrosarcoma
OT  - Extraskeletal myxoid chondrosarcoma
OT  - Sarcoma
OT  - Sunitinib
EDAT- 2014/04/08 06:00
MHDA- 2014/07/06 06:00
CRDT- 2014/04/08 06:00
PHST- 2014/02/28 00:00 [received]
PHST- 2014/03/07 00:00 [revised]
PHST- 2014/03/11 00:00 [accepted]
PHST- 2014/04/08 06:00 [entrez]
PHST- 2014/04/08 06:00 [pubmed]
PHST- 2014/07/06 06:00 [medline]
AID - S0959-8049(14)00256-1 [pii]
AID - 10.1016/j.ejca.2014.03.013 [doi]
PST - ppublish
SO  - Eur J Cancer. 2014 Jun;50(9):1657-64. doi: 10.1016/j.ejca.2014.03.013. Epub 2014 
      Apr 2.