Preclinical and clinical evidence of activity of pazopanib in solitary fibrous tumour

Eur J Cancer. 2014 Nov;50(17):3021-8. doi: 10.1016/j.ejca.2014.09.004. Epub 2014 Sep 27.

Abstract

Background: To explore the activity of pazopanib in solitary fibrous tumour (SFT).

Patients and 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.

Keywords: Chemotherapy; Pazopanib; Sarcoma; Solitary fibrous tumour; Sunitinib; Tyrosine kinase.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacology*
  • Axitinib
  • Bevacizumab
  • Humans
  • Imidazoles / pharmacology
  • Indazoles / pharmacology
  • Indoles / pharmacology
  • MAP Kinase Signaling System / physiology
  • Male
  • Mice, SCID
  • Middle Aged
  • Neoplasm Transplantation
  • Niacinamide / analogs & derivatives
  • Niacinamide / pharmacology
  • Phenylurea Compounds / pharmacology
  • Pyridines / pharmacology
  • Pyrimidines / administration & dosage
  • Pyrimidines / pharmacology*
  • Pyrroles / pharmacology
  • Receptor, Platelet-Derived Growth Factor beta / metabolism
  • Solitary Fibrous Tumors / drug therapy*
  • Sorafenib
  • Sulfonamides / administration & dosage
  • Sulfonamides / pharmacology*
  • Sunitinib
  • Transplantation, Heterologous
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Imidazoles
  • Indazoles
  • Indoles
  • Phenylurea Compounds
  • Pyridines
  • Pyrimidines
  • Pyrroles
  • Sulfonamides
  • regorafenib
  • Niacinamide
  • Bevacizumab
  • pazopanib
  • Sorafenib
  • Axitinib
  • Receptor, Platelet-Derived Growth Factor beta
  • Vascular Endothelial Growth Factor Receptor-2
  • Sunitinib