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

S Stacchiotti, M Saponara, R Frapolli, M Tortoreto, D Cominetti, S Provenzano, T Negri, G P Dagrada, A Gronchi, C Colombo, B Vincenzi, G Badalamenti, V Zuco, S L Renne, P Collini, C Morosi, A P Dei Tos, E Bello, S Pilotti, P G CasaliM D'Incalci, N Zaffaroni

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)84-92
Number of pages9
JournalEuropean Journal of Cancer
Volume76
DOIs
Publication statusPublished - May 2017

Keywords

  • Adult
  • Aged
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols
  • Blotting, Western
  • Cerebellar Neoplasms
  • Dacarbazine
  • Dioxoles
  • Disease-Free Survival
  • Doxorubicin
  • Female
  • Furans
  • Humans
  • Ifosfamide
  • Ketones
  • Kidney Neoplasms
  • Male
  • Meningeal Neoplasms
  • Mice, 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
  • Journal Article

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this