Clinical activity of regorafenib in elderly patients with recurrent glioblastoma

Fasano, Morena; Pirozzi, Mario; Famiglietti, Vincenzo; Facchini, Sergio; Caterino, Marianna; Caroprese, Mara; Barillaro, Angela; Giovanni, Ilaria Di; Auriemma, Annunziata; Fattoruso, Silvia Ileana; Somma, Teresa; Solari, Domenico; Bocchetti, Marco; Conson, Manuel; Pacelli, Roberto; Addeo, Raffaele

doi:10.3892/mco.2023.2605

Cited by 3 publications

(2 citation statements)

References 37 publications

(54 reference statements)

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“…The REGOMA phase II randomized trial (NCT02926222) showed a small mOS benefit of regorafenib (7.4 months) versus lomustine treatment (5.6 months) [ 454 , 551 ]. Age and MGMT methylation appeared to influence OS, thus suggesting that regorafenib treatment could be an alternative in older patients [ 552 ]. Regorafenib (phase II/III trial, NCT03970447) has not received the EMA approval, although it is the first-choice treatment for rGB according to Italian Association of Medical Oncology guidelines [ 553 , 554 ].…”

Section: Targeted Therapiesmentioning

confidence: 99%

Glioblastoma Therapy: Past, Present and Future

Obrador,

Moreno-Murciano,

Oriol-Caballo

et al. 2024

IJMS

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Glioblastoma (GB) stands out as the most prevalent and lethal form of brain cancer. Although great efforts have been made by clinicians and researchers, no significant improvement in survival has been achieved since the Stupp protocol became the standard of care (SOC) in 2005. Despite multimodality treatments, recurrence is almost universal with survival rates under 2 years after diagnosis. Here, we discuss the recent progress in our understanding of GB pathophysiology, in particular, the importance of glioma stem cells (GSCs), the tumor microenvironment conditions, and epigenetic mechanisms involved in GB growth, aggressiveness and recurrence. The discussion on therapeutic strategies first covers the SOC treatment and targeted therapies that have been shown to interfere with different signaling pathways (pRB/CDK4/RB1/P16ink4, TP53/MDM2/P14arf, PI3k/Akt-PTEN, RAS/RAF/MEK, PARP) involved in GB tumorigenesis, pathophysiology, and treatment resistance acquisition. Below, we analyze several immunotherapeutic approaches (i.e., checkpoint inhibitors, vaccines, CAR-modified NK or T cells, oncolytic virotherapy) that have been used in an attempt to enhance the immune response against GB, and thereby avoid recidivism or increase survival of GB patients. Finally, we present treatment attempts made using nanotherapies (nanometric structures having active anti-GB agents such as antibodies, chemotherapeutic/anti-angiogenic drugs or sensitizers, radionuclides, and molecules that target GB cellular receptors or open the blood–brain barrier) and non-ionizing energies (laser interstitial thermal therapy, high/low intensity focused ultrasounds, photodynamic/sonodynamic therapies and electroporation). The aim of this review is to discuss the advances and limitations of the current therapies and to present novel approaches that are under development or following clinical trials.

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Section: Targeted Therapiesmentioning

confidence: 99%

Glioblastoma Therapy: Past, Present and Future

Obrador,

Moreno-Murciano,

Oriol-Caballo

et al. 2024

IJMS

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“…The issue of the role of age on response to regorafenib was analysed by Fasano et al too (Ref. 27 ). They reported the result of a retrospective study on recurrent GBM patients treated with regorafenib.…”

Section: Introductionmentioning

confidence: 99%

Regorafenib and glioblastoma: a literature review of preclinical studies, molecular mechanisms and clinical effectiveness

Mongiardi,

Pallini,

D'Alessandris

et al. 2024

Expert Rev. Mol. Med.

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Glioblastoma IDH wild type (GBM) is a very aggressive brain tumour, characterised by an infiltrative growth pattern and by a prominent neoangiogenesis. Its prognosis is unfortunately dismal, and the median overall survival of GBM patients is short (15 months). Clinical management is based on bulk tumour removal and standard chemoradiation with the alkylating drug temozolomide, but the tumour invariably recurs leading to patient's death. Clinical options for GBM patients remained unaltered for almost two decades until the encouraging results obtained by the phase II REGOMA trial allowed the introduction of the multikinase inhibitor regorafenib as a preferred regimen in relapsed GBM treatment by the National Comprehensive Cancer Network (NCCN) 2020 Guideline. Regorafenib, a sorafenib derivative, targets kinases associated with angiogenesis (VEGFR 1-3), as well as oncogenesis (c-KIT, RET, FGFR) and stromal kinases (FGFR, PDGFR-b). It was already approved for metastatic colorectal cancers and hepatocellular carcinomas. The aim of the present review is to focus on both the molecular and clinical knowledge collected in these first three years of regorafenib use in GBM.

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