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
Abstract 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 t...
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| Veröffentlicht in: | European journal of cancer (1990) 2017-05, Vol.76, p.84-92 |
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| creator | Stacchiotti, S Saponara, M Frapolli, R Tortoreto, M Cominetti, D Provenzano, S Negri, T Dagrada, G.P Gronchi, A Colombo, C Vincenzi, B Badalamenti, G Zuco, V Renne, S.L Collini, P Morosi, C Dei Tos, A.P Bello, E Pilotti, S Casali, P.G D'Incalci, M Zaffaroni, N |
| description | Abstract 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 patients' 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. |
| doi_str_mv | 10.1016/j.ejca.2017.02.002 |
| format | Article |
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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 patients' 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.</description><identifier>ISSN: 0959-8049</identifier><identifier>EISSN: 1879-0852</identifier><identifier>DOI: 10.1016/j.ejca.2017.02.002</identifier><identifier>PMID: 28284173</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject><![CDATA[Adult ; Aged ; Animal models ; Animals ; Anthracycline ; Anticancer properties ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Blotting, Western ; Cerebellar Neoplasms - drug therapy ; Cerebellar Neoplasms - mortality ; Chemotherapy ; Clinical trials ; Dacarbazine ; Dacarbazine - administration & dosage ; Dioxoles - administration & dosage ; Disease-Free Survival ; Doxorubicin ; Doxorubicin - administration & dosage ; Drug therapy ; Drugs ; Eribulin ; Female ; Furans - administration & dosage ; Hematology, Oncology and Palliative Medicine ; Humans ; Ifosfamide ; Ifosfamide - administration & dosage ; Immunodeficiency ; In vivo methods and tests ; Ketones - administration & dosage ; Kidney Neoplasms - drug therapy ; Kidney Neoplasms - mortality ; Male ; Mathematical models ; Meningeal Neoplasms - drug therapy ; Meningeal Neoplasms - mortality ; Metastasis ; Mice ; Mice model ; Mice, SCID ; Middle Aged ; Patients ; Pleural Neoplasms - drug therapy ; Pleural Neoplasms - mortality ; Progressions ; Response Evaluation Criteria in Solid Tumors ; Retroperitoneal Neoplasms - drug therapy ; Retroperitoneal Neoplasms - mortality ; Retrospective Studies ; Sarcoma ; Soft Tissue Neoplasms - drug therapy ; Soft Tissue Neoplasms - mortality ; Solitary Fibrous Tumors - drug therapy ; Solitary Fibrous Tumors - mortality ; Solitary fibrous tumour ; Studies ; Survival ; Survival Rate ; Tetrahydroisoquinolines - administration & dosage ; Trabectedin ; Treatment ; Tumors ; Xenograft ; Xenograft Model Antitumor Assays ; Xenografts ; Xenotransplantation]]></subject><ispartof>European journal of cancer (1990), 2017-05, Vol.76, p.84-92</ispartof><rights>Elsevier Ltd</rights><rights>2017 Elsevier Ltd</rights><rights>Copyright © 2017 Elsevier Ltd. All rights reserved.</rights><rights>Copyright Elsevier Science Ltd. May 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c483t-c960bd7e5c73d2aa0d6d5c553bb85250f56b706b1b63941e16dca4435b012e5c3</citedby><cites>FETCH-LOGICAL-c483t-c960bd7e5c73d2aa0d6d5c553bb85250f56b706b1b63941e16dca4435b012e5c3</cites><orcidid>0000-0002-1742-8666 ; 0000-0002-4669-0890 ; 0000-0002-2478-8838 ; 0000-0003-1324-6432</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S095980491730727X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28284173$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Stacchiotti, S</creatorcontrib><creatorcontrib>Saponara, M</creatorcontrib><creatorcontrib>Frapolli, R</creatorcontrib><creatorcontrib>Tortoreto, M</creatorcontrib><creatorcontrib>Cominetti, D</creatorcontrib><creatorcontrib>Provenzano, S</creatorcontrib><creatorcontrib>Negri, T</creatorcontrib><creatorcontrib>Dagrada, G.P</creatorcontrib><creatorcontrib>Gronchi, A</creatorcontrib><creatorcontrib>Colombo, C</creatorcontrib><creatorcontrib>Vincenzi, B</creatorcontrib><creatorcontrib>Badalamenti, G</creatorcontrib><creatorcontrib>Zuco, V</creatorcontrib><creatorcontrib>Renne, S.L</creatorcontrib><creatorcontrib>Collini, P</creatorcontrib><creatorcontrib>Morosi, C</creatorcontrib><creatorcontrib>Dei Tos, A.P</creatorcontrib><creatorcontrib>Bello, E</creatorcontrib><creatorcontrib>Pilotti, S</creatorcontrib><creatorcontrib>Casali, P.G</creatorcontrib><creatorcontrib>D'Incalci, M</creatorcontrib><creatorcontrib>Zaffaroni, N</creatorcontrib><title>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</title><title>European journal of cancer (1990)</title><addtitle>Eur J Cancer</addtitle><description>Abstract 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 patients' 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.</description><subject>Adult</subject><subject>Aged</subject><subject>Animal models</subject><subject>Animals</subject><subject>Anthracycline</subject><subject>Anticancer properties</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Blotting, Western</subject><subject>Cerebellar Neoplasms - drug therapy</subject><subject>Cerebellar Neoplasms - mortality</subject><subject>Chemotherapy</subject><subject>Clinical trials</subject><subject>Dacarbazine</subject><subject>Dacarbazine - administration & dosage</subject><subject>Dioxoles - administration & dosage</subject><subject>Disease-Free Survival</subject><subject>Doxorubicin</subject><subject>Doxorubicin - administration & dosage</subject><subject>Drug therapy</subject><subject>Drugs</subject><subject>Eribulin</subject><subject>Female</subject><subject>Furans - administration & dosage</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Humans</subject><subject>Ifosfamide</subject><subject>Ifosfamide - administration & dosage</subject><subject>Immunodeficiency</subject><subject>In vivo methods and tests</subject><subject>Ketones - administration & dosage</subject><subject>Kidney Neoplasms - drug therapy</subject><subject>Kidney Neoplasms - mortality</subject><subject>Male</subject><subject>Mathematical models</subject><subject>Meningeal Neoplasms - drug therapy</subject><subject>Meningeal Neoplasms - mortality</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Mice model</subject><subject>Mice, SCID</subject><subject>Middle Aged</subject><subject>Patients</subject><subject>Pleural Neoplasms - drug therapy</subject><subject>Pleural Neoplasms - mortality</subject><subject>Progressions</subject><subject>Response Evaluation Criteria in Solid Tumors</subject><subject>Retroperitoneal Neoplasms - drug therapy</subject><subject>Retroperitoneal Neoplasms - mortality</subject><subject>Retrospective Studies</subject><subject>Sarcoma</subject><subject>Soft Tissue Neoplasms - drug therapy</subject><subject>Soft Tissue Neoplasms - mortality</subject><subject>Solitary Fibrous Tumors - drug therapy</subject><subject>Solitary Fibrous Tumors - mortality</subject><subject>Solitary fibrous tumour</subject><subject>Studies</subject><subject>Survival</subject><subject>Survival Rate</subject><subject>Tetrahydroisoquinolines - administration & dosage</subject><subject>Trabectedin</subject><subject>Treatment</subject><subject>Tumors</subject><subject>Xenograft</subject><subject>Xenograft Model Antitumor Assays</subject><subject>Xenografts</subject><subject>Xenotransplantation</subject><issn>0959-8049</issn><issn>1879-0852</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UstqFEEUbUQxk-gPuJACN256Uo9-gggh-IKAggruinr1zB17qsaq6iHj7-ZHvJ1JssjCRdNN1Tnnnj73FMUrRpeMsuZ8s3Qbo5acsnZJ-ZJS_qRYsK7tS9rV_GmxoH3dlx2t-pPiNKUNpbTtKvq8OOEd7yrWikVx801lcD6X1kXYO0tSGCGreCAD6BimRPK0DVMk186HVVRDTmQXnQWTyRpWa5KcT5BhD_lAciA2XIc4aTDgz60yKmr1F7wjJmw1eJwVPH77AeIWh4EneY2XI3gwRHl7qznik28vdiGjN1AjccPgDI5x3qVEwkByVBpP0IknIRJ0ryeUIWqlwKeZDvfeXxTPBjUm9_LufVb8_Pjhx-Xn8urrpy-XF1elqTqRS9M3VNvW1aYVlitFbWNrU9dCa4yzpkPd6JY2mulG9BVzrLFGVZWoNWUcWeKseHvU3cXwZ3Ipyy0k48ZReYdJSlxN07G2EgKhbx5BN2jUozvJqWCibQTrEcWPKBNDStENchdhi8uRjMq5AnIj5wrIuQKScokVQNLrO-lJY8YPlPudI-DdEeAwiz24KJPBChiMMmKi0gb4v_77R_Tj-tT42x1cevgPJhMS5Pe5hHMHcTRteftL_ANztd6j</recordid><startdate>20170501</startdate><enddate>20170501</enddate><creator>Stacchiotti, S</creator><creator>Saponara, M</creator><creator>Frapolli, R</creator><creator>Tortoreto, M</creator><creator>Cominetti, D</creator><creator>Provenzano, S</creator><creator>Negri, T</creator><creator>Dagrada, G.P</creator><creator>Gronchi, A</creator><creator>Colombo, C</creator><creator>Vincenzi, B</creator><creator>Badalamenti, G</creator><creator>Zuco, V</creator><creator>Renne, S.L</creator><creator>Collini, P</creator><creator>Morosi, C</creator><creator>Dei Tos, A.P</creator><creator>Bello, E</creator><creator>Pilotti, S</creator><creator>Casali, P.G</creator><creator>D'Incalci, M</creator><creator>Zaffaroni, N</creator><general>Elsevier Ltd</general><general>Elsevier Science Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TO</scope><scope>7U7</scope><scope>C1K</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-1742-8666</orcidid><orcidid>https://orcid.org/0000-0002-4669-0890</orcidid><orcidid>https://orcid.org/0000-0002-2478-8838</orcidid><orcidid>https://orcid.org/0000-0003-1324-6432</orcidid></search><sort><creationdate>20170501</creationdate><title>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</title><author>Stacchiotti, S ; Saponara, M ; Frapolli, R ; Tortoreto, M ; Cominetti, D ; Provenzano, S ; Negri, T ; Dagrada, G.P ; Gronchi, A ; Colombo, C ; Vincenzi, B ; Badalamenti, G ; Zuco, V ; Renne, S.L ; Collini, P ; Morosi, C ; Dei Tos, A.P ; Bello, E ; Pilotti, S ; Casali, P.G ; D'Incalci, M ; Zaffaroni, N</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c483t-c960bd7e5c73d2aa0d6d5c553bb85250f56b706b1b63941e16dca4435b012e5c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Animal models</topic><topic>Animals</topic><topic>Anthracycline</topic><topic>Anticancer properties</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Blotting, Western</topic><topic>Cerebellar Neoplasms - drug therapy</topic><topic>Cerebellar Neoplasms - mortality</topic><topic>Chemotherapy</topic><topic>Clinical trials</topic><topic>Dacarbazine</topic><topic>Dacarbazine - administration & dosage</topic><topic>Dioxoles - administration & dosage</topic><topic>Disease-Free Survival</topic><topic>Doxorubicin</topic><topic>Doxorubicin - administration & dosage</topic><topic>Drug therapy</topic><topic>Drugs</topic><topic>Eribulin</topic><topic>Female</topic><topic>Furans - administration & dosage</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Humans</topic><topic>Ifosfamide</topic><topic>Ifosfamide - administration & dosage</topic><topic>Immunodeficiency</topic><topic>In vivo methods and tests</topic><topic>Ketones - administration & dosage</topic><topic>Kidney Neoplasms - drug therapy</topic><topic>Kidney Neoplasms - mortality</topic><topic>Male</topic><topic>Mathematical models</topic><topic>Meningeal Neoplasms - drug therapy</topic><topic>Meningeal Neoplasms - mortality</topic><topic>Metastasis</topic><topic>Mice</topic><topic>Mice model</topic><topic>Mice, SCID</topic><topic>Middle Aged</topic><topic>Patients</topic><topic>Pleural Neoplasms - drug therapy</topic><topic>Pleural Neoplasms - mortality</topic><topic>Progressions</topic><topic>Response Evaluation Criteria in Solid Tumors</topic><topic>Retroperitoneal Neoplasms - drug therapy</topic><topic>Retroperitoneal Neoplasms - mortality</topic><topic>Retrospective Studies</topic><topic>Sarcoma</topic><topic>Soft Tissue Neoplasms - drug therapy</topic><topic>Soft Tissue Neoplasms - mortality</topic><topic>Solitary Fibrous Tumors - drug therapy</topic><topic>Solitary Fibrous Tumors - mortality</topic><topic>Solitary fibrous tumour</topic><topic>Studies</topic><topic>Survival</topic><topic>Survival Rate</topic><topic>Tetrahydroisoquinolines - administration & dosage</topic><topic>Trabectedin</topic><topic>Treatment</topic><topic>Tumors</topic><topic>Xenograft</topic><topic>Xenograft Model Antitumor Assays</topic><topic>Xenografts</topic><topic>Xenotransplantation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Stacchiotti, S</creatorcontrib><creatorcontrib>Saponara, M</creatorcontrib><creatorcontrib>Frapolli, R</creatorcontrib><creatorcontrib>Tortoreto, M</creatorcontrib><creatorcontrib>Cominetti, D</creatorcontrib><creatorcontrib>Provenzano, S</creatorcontrib><creatorcontrib>Negri, T</creatorcontrib><creatorcontrib>Dagrada, G.P</creatorcontrib><creatorcontrib>Gronchi, A</creatorcontrib><creatorcontrib>Colombo, C</creatorcontrib><creatorcontrib>Vincenzi, B</creatorcontrib><creatorcontrib>Badalamenti, G</creatorcontrib><creatorcontrib>Zuco, V</creatorcontrib><creatorcontrib>Renne, S.L</creatorcontrib><creatorcontrib>Collini, P</creatorcontrib><creatorcontrib>Morosi, C</creatorcontrib><creatorcontrib>Dei Tos, A.P</creatorcontrib><creatorcontrib>Bello, E</creatorcontrib><creatorcontrib>Pilotti, S</creatorcontrib><creatorcontrib>Casali, P.G</creatorcontrib><creatorcontrib>D'Incalci, M</creatorcontrib><creatorcontrib>Zaffaroni, N</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of cancer (1990)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stacchiotti, S</au><au>Saponara, M</au><au>Frapolli, R</au><au>Tortoreto, M</au><au>Cominetti, D</au><au>Provenzano, S</au><au>Negri, T</au><au>Dagrada, G.P</au><au>Gronchi, A</au><au>Colombo, C</au><au>Vincenzi, B</au><au>Badalamenti, G</au><au>Zuco, V</au><au>Renne, S.L</au><au>Collini, P</au><au>Morosi, C</au><au>Dei Tos, A.P</au><au>Bello, E</au><au>Pilotti, S</au><au>Casali, P.G</au><au>D'Incalci, M</au><au>Zaffaroni, N</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>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</atitle><jtitle>European journal of cancer (1990)</jtitle><addtitle>Eur J Cancer</addtitle><date>2017-05-01</date><risdate>2017</risdate><volume>76</volume><spage>84</spage><epage>92</epage><pages>84-92</pages><issn>0959-8049</issn><eissn>1879-0852</eissn><abstract>Abstract 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 patients' 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.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>28284173</pmid><doi>10.1016/j.ejca.2017.02.002</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-1742-8666</orcidid><orcidid>https://orcid.org/0000-0002-4669-0890</orcidid><orcidid>https://orcid.org/0000-0002-2478-8838</orcidid><orcidid>https://orcid.org/0000-0003-1324-6432</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0959-8049 |
| ispartof | European journal of cancer (1990), 2017-05, Vol.76, p.84-92 |
| issn | 0959-8049 1879-0852 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1876817433 |
| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Adult Aged Animal models Animals Anthracycline Anticancer properties Antineoplastic Combined Chemotherapy Protocols - therapeutic use Blotting, Western Cerebellar Neoplasms - drug therapy Cerebellar Neoplasms - mortality Chemotherapy Clinical trials Dacarbazine Dacarbazine - administration & dosage Dioxoles - administration & dosage Disease-Free Survival Doxorubicin Doxorubicin - administration & dosage Drug therapy Drugs Eribulin Female Furans - administration & dosage Hematology, Oncology and Palliative Medicine Humans Ifosfamide Ifosfamide - administration & dosage Immunodeficiency In vivo methods and tests Ketones - administration & dosage Kidney Neoplasms - drug therapy Kidney Neoplasms - mortality Male Mathematical models Meningeal Neoplasms - drug therapy Meningeal Neoplasms - mortality Metastasis Mice Mice model Mice, SCID Middle Aged Patients Pleural Neoplasms - drug therapy Pleural Neoplasms - mortality Progressions Response Evaluation Criteria in Solid Tumors Retroperitoneal Neoplasms - drug therapy Retroperitoneal Neoplasms - mortality Retrospective Studies Sarcoma Soft Tissue Neoplasms - drug therapy Soft Tissue Neoplasms - mortality Solitary Fibrous Tumors - drug therapy Solitary Fibrous Tumors - mortality Solitary fibrous tumour Studies Survival Survival Rate Tetrahydroisoquinolines - administration & dosage Trabectedin Treatment Tumors Xenograft Xenograft Model Antitumor Assays Xenografts Xenotransplantation |
| title | 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 |
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