Abstract
Background
Glioblastoma is the most common and aggressive primary brain tumor in adults.The aggressiveness and poor prognosis related to this disease join to the limited available treatment options. The current standard of care involves surgical resection followed by concomitant radiotherapy and chemotherapy. At recurrence, no standard treatment exists and there are no guidelines to facilitate decisions in the recurrent setting. Available options include re-operation, re-irradiation, systemic therapy, alone or in combination. In recent years, immunotherapy strategies have revolutionized the treatment of many cancers, increasing the hope for GBM therapy. Regorafenib (Stivarga) is an inhibitor of several kinases involved in the mechanisms that regulate neoangiogenesis processes, through the inhibition vascular endothelial growth factor (VEGF) receptors and the modifications of the tumor microenvironment; specifically, Regorafenib binds an d stabilizes PSAT1 (phosphoserine aminotransferase 1). The dual regulatory mechanism underlying PSAT1-induced autophagy arrest accounts for the superior anti-GBM effect of Regorafenib compared with Temozolomide.
Material and Methods
15 patients with documented disease progression after surgery followed by RT and TMZ were assigned to receive regorafenib (REG) 160 mg once daily for the first 3 weeks of each 4-week cycle. All patients received prior radiation therapy (RT) to a median dose of 60 Gy (range 40.05 -60). Median time to retreatment after prior RT was 16 months (range 14-33). Tumor volumes ranged from 81.7 cm3 to 422.4 cm3 (CTV) and from 112.7 cm3 to 422.4 cm3 (PTV).3 patients (20%) received concomitant reirradiation with a radiation dose of 37.5 Gy in 15 fractions of 2.5 Gy.
Results
the median follow-up was 9.5 months (range 5-22). The overall survival and the progression-free survival rates were 53,8 %, and 46,6 % respectively at 2 years. In 53% the sympto ms were stable. Only one patient developed late toxicity: acute pancreatitis (Grade I) regressed on interruption of Regorafenib. No other neurological deficits occurred during follow-up. At last follow up 60% of patients were alive.
Conclusion
we report our experience with Regorafenib, administered in patients with rapid progression after the end of postoperative radio chemotherapy treatment. Regorafenib might be a new potential treatment option for recurrent glioblastoma: it was well tolerated also in cases of combined treatment with reirradiation and appeared effective. Other studies will be necessary to evaluate and confirm the role of Regorafenib in glioblastoma patients and the potential effectiveness of the combined therapeutic strategy: Regorafenib-reirradiation.
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