er-086526 and Retroperitoneal-Neoplasms

Retroperitoneal sarcomas are extremely rare malignant tumors. The most common type of sarcomas arising in the retroperitoneum are liposarcomas, occurring mostly in the sixth and seventh decades of life. The only potentially curative approach to liposarcomas is the complete surgical resection of the tumor with negative microscopic margins. However, retroperitoneal liposarcomas exhibit a propensity for local recurrence and distant metastasis despite the negative surgical margins, thus requiring additional therapy. Eribulin demonstrated a benefit in terms of overall survival in patients with advanced or metastatic liposarcoma. We report two cases of patients, both submitted to concomitant right nephrectomy, who experienced a long-lasting control of recurrent retroperitoneal liposarcoma before being submitted to eribulin-based therapeutic regimens (23 and 24 treatment cycles completed, respectively).

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Duration of Therapy; Furans; Humans; Ketones; Liposarcoma; Magnetic Resonance Imaging; Male; Nephrectomy; Positron Emission Tomography Computed Tomography; Retroperitoneal Neoplasms; Solitary Kidney; Tomography, X-Ray Computed; Treatment Outcome

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.. 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.. 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.. 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.

Topics: 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; Trabectedin; Xenograft Model Antitumor Assays