title: Response of brain metastasis from lung cancer patients to an oral nutraceutical product containing silibinin.
abstract: Despite multimodal treatment approaches, the prognosis of brain metastases (BM) from non-small cell lung cancer (NSCLC) remains poor. Untreated patients with BM have a median survival of about 1 month, with almost all patients dying from neurological causes. We herein present the first report describing the response of BM from NSCLC patients to an oral nutraceutical product containing silibinin, a flavonoid extracted from the seeds of the milk thistle. We present evidence of how the use of the silibinin-based nutraceutical Legasil® resulted in significant clinical and radiological improvement of BM from NSCLC patients with poor performance status that progressed after whole brain radiotherapy and chemotherapy. The suppressive effects of silibinin on progressive BM, which involved a marked reduction of the peritumoral brain edema, occurred without affecting the primary lung tumor outgrowth in NSCLC patients. Because BM patients have an impaired survival prognosis and are in need for an immediate tumor control, the combination of brain radiotherapy with silibinin-based nutraceuticals might not only alleviate BM edema but also prove local control and time for either classical chemotherapeutics with immunostimulatory effects or new immunotherapeutic agents such as checkpoint blockers to reveal their full therapeutic potential in NSCLC BM patients. New studies aimed to illuminate the mechanistic aspects underlying the regulatory effects of silibinin on the cellular and molecular pathobiology of BM might expedite the entry of new formulations of silibinin into clinical testing for progressive BM from lung cancer patients.
authors.affiliation: Department of Medical Oncology, Catalan Institute of Oncology, Doctor Josep Trueta University Hospital, Girona, Spain.|Girona Biomedical Research Institute (IDIBGi), Girona, Spain.|Department of Medical Sciences, Medical School, University of Girona, Girona, Spain.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Bosch-Barrera
authors.affiliation: Department of Medical Oncology, Catalan Institute of Oncology, Doctor Josep Trueta University Hospital, Girona, Spain.
authors.forename: Elia
authors.initials: E
authors.lastname: Sais
authors.affiliation: Girona Biomedical Research Institute (IDIBGi), Girona, Spain.|Department of Radiology, Diagnostic Imaging Institute, Doctor Josep Trueta University Hospital, Girona, Spain.
authors.forename: Noemí
authors.initials: N
authors.lastname: Cañete
authors.affiliation: Girona Biomedical Research Institute (IDIBGi), Girona, Spain.|Department of Radiotherapy, Catalan Institute of Oncology, Doctor Josep Trueta University Hospital, Girona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Marruecos
authors.affiliation: Girona Biomedical Research Institute (IDIBGi), Girona, Spain.|ProCURE (Program Against Cancer Therapeutic Resistance), Metabolism and Cancer Group, Catalan Institute of Oncology, Girona, Spain.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Cuyàs
authors.affiliation: Department of Medical Oncology, Catalan Institute of Oncology, Doctor Josep Trueta University Hospital, Girona, Spain.|Girona Biomedical Research Institute (IDIBGi), Girona, Spain.|Department of Medical Sciences, Medical School, University of Girona, Girona, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Izquierdo
authors.affiliation: Department of Medical Oncology, Catalan Institute of Oncology, Doctor Josep Trueta University Hospital, Girona, Spain.|Girona Biomedical Research Institute (IDIBGi), Girona, Spain.|Department of Medical Sciences, Medical School, University of Girona, Girona, Spain.
authors.forename: Rut
authors.initials: R
authors.lastname: Porta
authors.affiliation: Girona Biomedical Research Institute (IDIBGi), Girona, Spain.|Department of Medical Sciences, Medical School, University of Girona, Girona, Spain.|Department of Pneumology, Doctor Josep Trueta University Hospital, Girona, Spain.
authors.forename: Manel
authors.initials: M
authors.lastname: Haro
authors.affiliation: Department of Medical Oncology, Catalan Institute of Oncology, Doctor Josep Trueta University Hospital, Girona, Spain.|Girona Biomedical Research Institute (IDIBGi), Girona, Spain.|Department of Medical Sciences, Medical School, University of Girona, Girona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Brunet
authors.affiliation: Girona Biomedical Research Institute (IDIBGi), Girona, Spain.|Department of Medical Sciences, Medical School, University of Girona, Girona, Spain.|Department of Radiology, Diagnostic Imaging Institute, Doctor Josep Trueta University Hospital, Girona, Spain.
authors.forename: Salvador
authors.initials: S
authors.lastname: Pedraza
authors.affiliation: Girona Biomedical Research Institute (IDIBGi), Girona, Spain.|ProCURE (Program Against Cancer Therapeutic Resistance), Metabolism and Cancer Group, Catalan Institute of Oncology, Girona, Spain.
authors.forename: Javier A
authors.initials: JA
authors.lastname: Menendez
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects; D001929:Brain Edema / Q000175:diagnosis / Q000517:prevention & control; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000556:secondary*; D057176:Compassionate Use Trials; D019587:Dietary Supplements / Q000009:adverse effects; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D000077385:Silybin; D012838:Silymarin / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D012838:Silymarin; D000077385:Silybin
keywords: Legasil; STAT3; brain metastasis; non-small cell lung cancer; silibinin