TY - JOUR
T1 - Patient-derived solitary fibrous tumour xenografts predict high sensitivity to doxorubicin/dacarbazine combination confirmed in the clinic and highlight the potential effectiveness of trabectedin or eribulin against this tumour
AU - Dagrada, null
AU - Bello, null
AU - Saponara, Maristella
AU - Colombo, Chiara
AU - Morosi, null
AU - Casali, Paolo
AU - Cominetti, null
AU - Provenzano, Salvatore
AU - Renne, null
AU - Negri, null
AU - Gronchi, null
AU - Dei Tos, Angelo P.
AU - Badalamenti, null
AU - Frapolli, null
AU - Stacchiotti, null
AU - Tortoreto, Monica
AU - Zuco, Valentina
AU - Collini, Paola
AU - Vincenzi, Bruno
AU - Zaffaroni, Nadia
AU - D'Incalci, Maurizio
AU - Pilotti, null
AU - Badalamenti, Giuseppe
PY - 2017
Y1 - 2017
N2 - Background Preclinical models that mimic pathological and molecular features of solitary fibrous tumour (SFT) represent an important tool to select effective regimes and novel compounds to be tested in the clinic. This study was aimed at developing two preclinical models of SFT, assessing their predictive value in the clinic and selecting potential novel effective treatments. Material and methods Two dedifferentiated-SFT (D-SFT) models obtained from patientsâ biopsies were grown in immunodeficient mice. The antitumour activity on these models of doxorubicin, dacarbazine (DTIC), ifosfamide (monotherapy or combination), trabectedin and eribulin was tested. Twelve SFT patients were treated with doxorubicin and DTIC. Response by RECIST, progression-free survival and overall survival were retrospectively evaluated, distinguishing malignant-SFT (M-SFT) and D-SFT. Results Two D-SFT patient-derived xenografts (PDXs) that represent the first available preclinical in vivo models of SFT were developed and characterised. Doxorubicin/DTIC, DTIC/ifosfamide, doxorubicin/ifosfamide combinations consistently induced better antitumour activity than the single-agents. Particularly, doxorubicin/DTIC combination caused a max tumour volume inhibition >80% in both models. Doxorubicin/DTIC combo showed activity also in the case-series. Best RECIST responses were: 6 responses (M-SFT = 2 of 7, D-SFT = 4 of 5), 1 stable disease, 5 progressions, with a 6-month median progression-free survival (M-SFT = 6, D-SFT = 10 months). The PDXs were very sensitive to trabectedin and eribulin. Conclusion Doxorubicin plus DTIC combination was effective in our two D-SFT mice models and appeared to be active also in the clinic, especially in high-grade D-SFT patients. Among additional drugs tested in the PDXs, trabectedin and eribulin were highly effective, providing a rational to test these drugs in D-SFT patients.
AB - Background Preclinical models that mimic pathological and molecular features of solitary fibrous tumour (SFT) represent an important tool to select effective regimes and novel compounds to be tested in the clinic. This study was aimed at developing two preclinical models of SFT, assessing their predictive value in the clinic and selecting potential novel effective treatments. Material and methods Two dedifferentiated-SFT (D-SFT) models obtained from patientsâ biopsies were grown in immunodeficient mice. The antitumour activity on these models of doxorubicin, dacarbazine (DTIC), ifosfamide (monotherapy or combination), trabectedin and eribulin was tested. Twelve SFT patients were treated with doxorubicin and DTIC. Response by RECIST, progression-free survival and overall survival were retrospectively evaluated, distinguishing malignant-SFT (M-SFT) and D-SFT. Results Two D-SFT patient-derived xenografts (PDXs) that represent the first available preclinical in vivo models of SFT were developed and characterised. Doxorubicin/DTIC, DTIC/ifosfamide, doxorubicin/ifosfamide combinations consistently induced better antitumour activity than the single-agents. Particularly, doxorubicin/DTIC combination caused a max tumour volume inhibition >80% in both models. Doxorubicin/DTIC combo showed activity also in the case-series. Best RECIST responses were: 6 responses (M-SFT = 2 of 7, D-SFT = 4 of 5), 1 stable disease, 5 progressions, with a 6-month median progression-free survival (M-SFT = 6, D-SFT = 10 months). The PDXs were very sensitive to trabectedin and eribulin. Conclusion Doxorubicin plus DTIC combination was effective in our two D-SFT mice models and appeared to be active also in the clinic, especially in high-grade D-SFT patients. Among additional drugs tested in the PDXs, trabectedin and eribulin were highly effective, providing a rational to test these drugs in D-SFT patients.
KW - Anthracycline; Chemotherapy; Dacarbazine; Doxorubicin; Eribulin; Ifosfamide; Metastasis; Mice model; Sarcoma; Solitary fibrous tumour; Trabectedin; Treatment; Xenograft; Adult; Aged; Animals; Antineoplastic Combined Chemotherapy Protocols; Blotting
KW - SCID; Middle Aged; Pleural Neoplasms; Response Evaluation Criteria in Solid Tumors; Retroperitoneal Neoplasms; Retrospective Studies; Soft Tissue Neoplasms; Solitary Fibrous Tumors; Survival Rate; Tetrahydroisoquinolines; Xenograft Model Antitumor Assays;
KW - Western; Cerebellar Neoplasms; Dacarbazine; Dioxoles; Disease-Free Survival; Doxorubicin; Female; Furans; Humans; Ifosfamide; Ketones; Kidney Neoplasms; Male; Meningeal Neoplasms; Mice
KW - Anthracycline; Chemotherapy; Dacarbazine; Doxorubicin; Eribulin; Ifosfamide; Metastasis; Mice model; Sarcoma; Solitary fibrous tumour; Trabectedin; Treatment; Xenograft; Adult; Aged; Animals; Antineoplastic Combined Chemotherapy Protocols; Blotting
KW - SCID; Middle Aged; Pleural Neoplasms; Response Evaluation Criteria in Solid Tumors; Retroperitoneal Neoplasms; Retrospective Studies; Soft Tissue Neoplasms; Solitary Fibrous Tumors; Survival Rate; Tetrahydroisoquinolines; Xenograft Model Antitumor Assays;
KW - Western; Cerebellar Neoplasms; Dacarbazine; Dioxoles; Disease-Free Survival; Doxorubicin; Female; Furans; Humans; Ifosfamide; Ketones; Kidney Neoplasms; Male; Meningeal Neoplasms; Mice
UR - http://hdl.handle.net/10447/248299
UR - http://www.journals.elsevier.com/european-journal-of-cancer/
M3 - Article
VL - 76
SP - 84
EP - 92
JO - European Journal of Cancer
JF - European Journal of Cancer
SN - 0959-8049
ER -