title: Preclinical and clinical evidence of activity of pazopanib in solitary fibrous tumour.
abstract: BACKGROUND
  To explore the activity of pazopanib in solitary fibrous tumour (SFT).
  
  
  METHODS
  In a preclinical study, we compared the activity of pazopanib, sorafenib, sunitinib, regorafenib, axitinib and bevacizumab in a dedifferentiated-SFT (DSFT) xenotransplanted into Severe Combined Immunodeficiency (SCID) mice. Antiangiogenics were administered at their reported optimal doses when mean tumour volume (TV) was 80 mm(3). Drug activity was assessed as TV inhibition percentage (TVI%). From May 2012, six consecutive patients with advanced SFT received pazopanib, on a national name-based programme. In one case sunitinib was administered after pazopanib failure.
  
  
  RESULTS
  In the xenograft model, pazopanib showed the lowest antitumour activity (21%TVI), while regorafenib was the most active (95%TVI). Sorafenib, bevacizumab, sunitinib were markedly active (78/70/65%TVI). Axitinib was marginally active (51%TVI). In the retrospective case-series, three patients carried malignant-SFT (MSFT), three DSFT. Best Response Evaluation Criteria in Solid Tumour (RECIST) responses were: three stable disease (SD), all MSFT, three progressive disease (PD), all DSFT, corresponding to one partial response (PR), two SD, three PD by Choi criteria. Median-progression-free survival was 3 months (range 1-15). In one patient, sunitinib was started after pazopanib failure, with a response.
  
  
  CONCLUSIONS
  In dedifferentiated-SFT xenograft pazopanib induced a marginal antitumour activity, while regorafenib appeared the most active and promising agent. When administered in patients, pazopanib showed a modest activity in terms of tumour growth stabilisation, observed only in non-dedifferentiated cases.
authors.affiliation: Adult Mesenchymal Tumor Medical Oncology Unit, Cancer Medicine Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy. Electronic address: silvia.stacchiotti@istitutotumori.mi.it.
authors.forename: S
authors.initials: S
authors.lastname: Stacchiotti
authors.affiliation: Molecular Pharmacology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Tortoreto
authors.affiliation: Medical Oncology Unit 'Sandro Pitigliani', S. Stefano Civil Hospital, Prato, Italy.
authors.forename: G G
authors.initials: GG
authors.lastname: Baldi
authors.affiliation: Medical Oncology, IRCCS - Istituto di Candiolo, Candiolo, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Grignani
authors.affiliation: Department of Oncology, Hematology and Respiratory Diseases, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Toss
authors.affiliation: Department of Oncology, University Hospital of Palermo, Palermo, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Badalamenti
authors.affiliation: Molecular Pharmacology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Cominetti
authors.affiliation: Department of Radiology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Morosi
authors.affiliation: Department of Anatomic Pathology, General Hospital of Treviso, Treviso, Italy.
authors.forename: A P
authors.initials: AP
authors.lastname: Dei Tos
authors.affiliation: Pharmacy Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Festinese
authors.affiliation: Adult Mesenchymal Tumor Medical Oncology Unit, Cancer Medicine Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Fumagalli
authors.affiliation: Adult Mesenchymal Tumor Medical Oncology Unit, Cancer Medicine Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Provenzano
authors.affiliation: Melanoma and Sarcoma Unit, Department of Surgery, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Gronchi
authors.affiliation: Melanoma and Sarcoma, Surgery Department, Istituto Europeo di Oncologia, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Pennacchioli
authors.affiliation: Laboratory of Experimental Molecular Pathology, Department of Diagnostic Pathology and Laboratory, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Negri
authors.affiliation: Laboratory of Experimental Molecular Pathology, Department of Diagnostic Pathology and Laboratory, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: G P
authors.initials: GP
authors.lastname: Dagrada
authors.affiliation: Laboratory of Experimental Molecular Pathology, Department of Diagnostic Pathology and Laboratory, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: R D
authors.initials: RD
authors.lastname: Spagnuolo
authors.affiliation: Laboratory of Experimental Molecular Pathology, Department of Diagnostic Pathology and Laboratory, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Pilotti
authors.affiliation: Adult Mesenchymal Tumor Medical Oncology Unit, Cancer Medicine Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: P G
authors.initials: PG
authors.lastname: Casali
authors.affiliation: Molecular Pharmacology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Zaffaroni
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000077784:Axitinib; D000068258:Bevacizumab; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007191:Indazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D016513:Mice, SCID; D008875:Middle Aged; D009368:Neoplasm Transplantation; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D010671:Phenylurea Compounds / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology*; D011758:Pyrroles / Q000494:pharmacology; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D054364:Solitary Fibrous Tumors / Q000188:drug therapy*; D000077157:Sorafenib; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*; D000077210:Sunitinib; D014183:Transplantation, Heterologous; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D007093:Imidazoles; D007191:Indazoles; D007211:Indoles; D010671:Phenylurea Compounds; D011725:Pyridines; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; C559147:regorafenib; D009536:Niacinamide; D000068258:Bevacizumab; C516667:pazopanib; D000077157:Sorafenib; D000077784:Axitinib; D020797:Receptor, Platelet-Derived Growth Factor beta; D040301:Vascular Endothelial Growth Factor Receptor-2; D000077210:Sunitinib
keywords: Chemotherapy; Pazopanib; Sarcoma; Solitary fibrous tumour; Sunitinib; Tyrosine kinase