Safety And Efficacy Of Silibinin In Patients With Brain Metastases after Radiosurgery: Sustain Trial
PO-1137
Abstract
Safety And Efficacy Of Silibinin In Patients With Brain Metastases after Radiosurgery: Sustain Trial
Authors: Isacco Desideri1, Luca Visani2, Viola Salvestrini1, Matteo Mariotti1, Marco Banini1, Lucia Angelini1, Maria Grazia Carnevale1, Ilaria Bonaparte1, Ludovica Zisca1, Beatrice Detti2, Daniela Greto2, Icro Meattini1, Lorenzo Livi1
1University of Florence, Radiation Oncology Unit, Florence, Italy; 2Azienda Ospedaliera Universitaria Careggi, Radiation Oncology Unit, Florence, Italy
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Purpose or Objective
Brain
metastases (BMs) develop in up to 30% of patients (pts) with cancer. Survival
of BMs pts is extremely variable and remarkably poor in absence of active
treatment. The use of stereotactic radiosurgery (SRS) for the treatment of BMs
has increased in recent years providing excellent local control rates even
though radiological assessment of the response to treatment can often be
challenging. Preclinical studies showed that silibinin - a natural polyphenolic
flavonoid isolated from seed extracts of the herb milk thistle - demonstrates
anticancer effects in vitro and in vivo. The use of a silibinin-based
nutraceutical resulted in significant clinical and radiological improvement of
BMs in non-small cell lung cancer (NSCLC) pts that progressed after whole brain
radiotherapy and chemotherapy. Thus, the aim of the present explorative study (SUSTAIN
trial) is to evaluate whether the use of silibinin-based nutraceuticals
(SILLBRAIN®) can significantly reduce distant brain failure (DBF) rate at 6
months in pts with first diagnosis of BMs treated with SRS with or without
surgery. Here a preliminary analysis on the first 18 pts enrolled is reported.
Material and Methods
SUSTAIN is a prospective,
single arm, phase II study planning to recruit a total of 80 pts with up to 10 BMs
from all primary
tumors (except small cell lung cancer), aged 18 or older, amenable for treatment with SRS or
surgery followed by SRS to cavity. Pts received 2 capsules (cps) of SILLBRAIN®
per day for the first month after SRS and 1 cp per day thereafter. The 6-month
DBF rate is assessed according to RANO criteria for brain metastases (RANO-BM).
Contrast-enhanced magnetic resonance (MRI) of the brain is performed at
baseline and every 12 weeks after SRS as per clinical practice. EORTC QLQ-C30
and BN20 questionnaires are administered at baseline and every 12 weeks after
SRS to evaluate health-related quality of life (HRQoL).
Results
At the time of this first analysis 18 pts have
been enrolled. The prevalent primary tumors were NSCLC and breast cancer, with 9
and 4 pts respectively. Ten pts had metachronous BMs onset, and 8 pts
synchronous. Nine pts received at least 1 line of systemic therapy and 17 pts
reported a controlled extracranial disease at BMs diagnosis. The overall number
of BMs was 55. All BMs were treated with SRS, with a median prescription dose
and median prescription isodose of 24Gy and 80%, respectively. According to
RANO-BM criteria, 1 pt reported distant intracranial failure with 3 months of
DBF. The median OS was 8 months. Only 1 pt discontinued SILLBRAIN® assumption
due to the onset of grade 1 nausea (CTCAE v5.0). No other adverse events were reported.
Conclusion
The addition
of silibinin-based nutraceuticals after SRS administration might improve
intracranial disease control in BMs pts, with a good safety profile. Final
results from SUSTAIN trial are awaited to confirm these encouraging findings.