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

S. Stacchiotti, M. Tortoreto, G. G. Baldi, G. Grignani, A. Toss, G. Badalamenti, D. Cominetti, C. Morosi, A. P. Dei Tos, F. Festinese, E. Fumagalli, S. Provenzano, A. Gronchi, E. Pennacchioli, T. Negri, G. P. Dagrada, R. D. Spagnuolo, S. Pilotti, P. G. Casali, N. Zaffaroni

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)3021-3028
Number of pages8
JournalEuropean Journal of Cancer
Volume50
Issue number17
DOIs
Publication statusPublished - 2014

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Solitary Fibrous Tumors
Tumor Burden
Heterografts
Severe Combined Immunodeficiency
pazopanib
Disease-Free Survival
Names
sunitinib

Keywords

  • Chemotherapy
  • Pazopanib
  • Sarcoma
  • Solitary fibrous tumour
  • Sunitinib
  • Tyrosine kinase

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Preclinical and clinical evidence of activity of pazopanib in solitary fibrous tumour. / Stacchiotti, S.; Tortoreto, M.; Baldi, G. G.; Grignani, G.; Toss, A.; Badalamenti, G.; Cominetti, D.; Morosi, C.; Dei Tos, A. P.; Festinese, F.; Fumagalli, E.; Provenzano, S.; Gronchi, A.; Pennacchioli, E.; Negri, T.; Dagrada, G. P.; Spagnuolo, R. D.; Pilotti, S.; Casali, P. G.; Zaffaroni, N.

In: European Journal of Cancer, Vol. 50, No. 17, 2014, p. 3021-3028.

Research output: Contribution to journalArticle

Stacchiotti, S, Tortoreto, M, Baldi, GG, Grignani, G, Toss, A, Badalamenti, G, Cominetti, D, Morosi, C, Dei Tos, AP, Festinese, F, Fumagalli, E, Provenzano, S, Gronchi, A, Pennacchioli, E, Negri, T, Dagrada, GP, Spagnuolo, RD, Pilotti, S, Casali, PG & Zaffaroni, N 2014, 'Preclinical and clinical evidence of activity of pazopanib in solitary fibrous tumour', European Journal of Cancer, vol. 50, no. 17, pp. 3021-3028. https://doi.org/10.1016/j.ejca.2014.09.004
Stacchiotti, S. ; Tortoreto, M. ; Baldi, G. G. ; Grignani, G. ; Toss, A. ; Badalamenti, G. ; Cominetti, D. ; Morosi, C. ; Dei Tos, A. P. ; Festinese, F. ; Fumagalli, E. ; Provenzano, S. ; Gronchi, A. ; Pennacchioli, E. ; Negri, T. ; Dagrada, G. P. ; Spagnuolo, R. D. ; Pilotti, S. ; Casali, P. G. ; Zaffaroni, N. / Preclinical and clinical evidence of activity of pazopanib in solitary fibrous tumour. In: European Journal of Cancer. 2014 ; Vol. 50, No. 17. pp. 3021-3028.
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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.",
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T1 - Preclinical and clinical evidence of activity of pazopanib in solitary fibrous tumour

AU - Stacchiotti, S.

AU - Tortoreto, M.

AU - Baldi, G. G.

AU - Grignani, G.

AU - Toss, A.

AU - Badalamenti, G.

AU - Cominetti, D.

AU - Morosi, C.

AU - Dei Tos, A. P.

AU - Festinese, F.

AU - Fumagalli, E.

AU - Provenzano, S.

AU - Gronchi, A.

AU - Pennacchioli, E.

AU - Negri, T.

AU - Dagrada, G. P.

AU - Spagnuolo, R. D.

AU - Pilotti, S.

AU - Casali, P. G.

AU - Zaffaroni, N.

PY - 2014

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N2 - 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.

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KW - Sarcoma

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