6533b856fe1ef96bd12b3008
RESEARCH PRODUCT
Preclinical and clinical evidence of activity of pazopanib in solitary fibrous tumour
Carlo MorosiElisabetta PennacchioliAlessandro GronchiAngela TossF. FestineseG.p. DagradaElena FumagalliRosalin Dolores SpagnuoloSilvia StacchiottiDenis CominettiGiuseppe BadalamentiGiovanni GrignaniNadia ZaffaroniMonica TortoretoPaolo G. CasaliGiacomo Giulio BaldiSalvatore ProvenzanoTiziana NegriS. PilottiA. P. Dei Tossubject
Chemotherapy; Pazopanib; Sarcoma; Solitary fibrous tumour; Sunitinib; Tyrosine kinase; Administration Oral; Adult; Aged; Angiogenesis Inhibitors; Animals; Antibodies Monoclonal Humanized; Antineoplastic Agents; Bevacizumab; Humans; Imidazoles; Indazoles; Indoles; MAP Kinase Signaling System; Male; Mice SCID; Middle Aged; Neoplasm Transplantation; Niacinamide; Phenylurea Compounds; Pyridines; Pyrimidines; Pyrroles; Receptor Platelet-Derived Growth Factor beta; Solitary Fibrous Tumors; Sulfonamides; Transplantation Heterologous; Vascular Endothelial Growth Factor Receptor-2; Cancer Research; Oncology; Medicine (all)OncologyMaleCancer ResearchIndolesAxitinibPyridinesPyridinemedicine.medical_treatmentSolitary fibrous tumourAdministration OralAngiogenesis InhibitorsMice SCIDPharmacologyPyrroleAntineoplastic Agentchemistry.chemical_compoundMiceSolitary Fibrous TumorChemotherapy; Pazopanib; Sarcoma; Solitary fibrous tumour; Sunitinib; Tyrosine kinase; Cancer Research; Oncology; Medicine (all)Transplantation HeterologouMonoclonalSunitinibHumanizedSulfonamidesHeterologousSunitinibMedicine (all)ImidazolesSarcomaMiddle AgedSorafenibPlatelet-Derived Growth Factor betaAxitinibBevacizumabOncologySolitary Fibrous TumorsAdministrationAngiogenesis InhibitorHumanmedicine.drugReceptorPhenylurea CompoundSorafenibOralAdultNiacinamidemedicine.medical_specialtyIndazolesBevacizumabMAP Kinase Signaling SystemTransplantation HeterologousAntineoplastic AgentsSulfonamideAntibodies Monoclonal HumanizedSCIDAntibodiesReceptor Platelet-Derived Growth Factor betaPazopanibInternal medicineRegorafenibmedicineAnimalsHumansChemotherapyPyrrolesImidazoleTyrosine kinaseAgedChemotherapyTransplantationAnimalbusiness.industryPhenylurea CompoundsPazopanibmedicine.diseaseChemotherapy; Pazopanib; Sarcoma; Solitary fibrous tumour; Sunitinib; Tyrosine kinase; Administration Oral; Adult; Aged; Angiogenesis Inhibitors; Animals; Antibodies Monoclonal Humanized; Antineoplastic Agents; Axitinib; Bevacizumab; Humans; Imidazoles; Indazoles; Indoles; MAP Kinase Signaling System; Male; Mice SCID; Middle Aged; Neoplasm Transplantation; Niacinamide; Phenylurea Compounds; Pyridines; Pyrimidines; Pyrroles; Receptor Platelet-Derived Growth Factor beta; Solitary Fibrous Tumors; Sorafenib; Sulfonamides; Sunitinib; Transplantation Heterologous; Vascular Endothelial Growth Factor Receptor-2Vascular Endothelial Growth Factor Receptor-2IndazolePyrimidinesPyrimidinechemistryIndolebusinessProgressive diseaseNeoplasm Transplantationdescription
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 mm3. 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2014-01-01 |