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 language | English |
|---|---|
| Pages (from-to) | 3021-3028 |
| Number of pages | 8 |
| Journal | European Journal of Cancer |
| Volume | 50 |
| Issue number | 17 |
| DOIs | |
| Publication status | Published - 2014 |
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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 journal › Article
}
TY - JOUR
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
Y1 - 2014
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.
AB - 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.
KW - Chemotherapy
KW - Pazopanib
KW - Sarcoma
KW - Solitary fibrous tumour
KW - Sunitinib
KW - Tyrosine kinase
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U2 - 10.1016/j.ejca.2014.09.004
DO - 10.1016/j.ejca.2014.09.004
M3 - Article
VL - 50
SP - 3021
EP - 3028
JO - European Journal of Cancer
JF - European Journal of Cancer
SN - 0959-8049
IS - 17
ER -