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Hepatocellular Carcinoma
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Daniel H. Palmer, Philip J. Johnson
Since FGF is an important alternative pathway of angiogenesis, it may contribute to resistance to VEGF-targeted drugs and thus brivanib, a VEGF and FGF receptor tyrosine kinase inhibitor, may have the potential to delay the emergence of such resistance. A large phase III trial of this drug also failed to improve outcomes compared with sorafenib.92 However, lenvatinib, another drug predominantly targeting VEGFRs and FGFRs, has been shown to be statistically non-inferior (but not superior) to sorafenib in terms of overall survival in a large phase III trial, such that lenvatinib has now also been approved as a standard of care for patients with advanced HCC (see Table 9.2).93 Although lenvatinib had superior efficacy for secondary outcome measures such as radiological response rate, progression-free survival, and time to progression, these did not appear to translate into measurable benefits in terms of quality of life, and there are currently no clear criteria to guide the choice between sorafenib and lenvatinib for individual patients. This study raises important questions for clinical trial design in advanced HCC in terms of the significance of secondary outcomes as surrogates of overall survival, the potential impact of post-progression therapy on OS as primary endpoint in an era of active second-line treatments (see below), and statistical design particularly in relation to non-inferiority as a pre-planned analysis.
Neuroendocrine tumors of the gastrointestinal tract
Published in Demetrius Pertsemlidis, William B. Inabnet III, Michel Gagner, Endocrine Surgery, 2017
Bernard Khoo, Tricia Tan, Stephen R. Bloom
Other angiogenesis inhibitors, such as sorafenib (a tyrosine kinase inhibitor of VEGFR2, PDGFRB, FGFR1, and FLT3) and bevacizumab (a monoclonal antibody against VEGF-A), have been shown to possess some promising activity against NETs in smaller trials. Pazopanib, brivanib, and cabozantinib are newer agents also targeting VEGF and VEGFR, which are currently under evaluation in trials [31].
Role of Medicinal Plants in Targeting Important Signaling Pathways in Cervical Cancer
Published in Anne George, Oluwatobi Samuel Oluwafemi, Blessy Joseph, Sabu Thomas, Sebastian Mathew, V. Raji, Holistic Healthcare, 2017
Savita Pandita, Rashmi Deshpande, Shama Aphale, Ruchika Kaul-Ghanekar
VEGF is a crucial factor involved in regulating angiogenesis that leads to progression of HPV induced cervical cancer.4,9 Many studies have demonstrated that its expression correlates with more aggressive tumors.82 VEGF inhibitors are agents that block the growth of malignant cells by inhibiting blood vessel formation through interference with signaling pathways involved in proliferation and metastasis of tumors. Currently bevacizumab, sunitinib, sorafenib, pazopanib, cediranib, brivanib, carboplatin, and paclitaxel with or without cediranib maleate are used as antiangiogenic drugs targeting VEGF pathway.22,65,83 The use of anti-VEGF drugs is limited due to their serious side effects, hence, the use of herbs could have significant potential.84 Various medicinal plants that have been shown to target VEGF pathway in cervical cancer include Camellia sinensis,22,85Curcuma longa,22,78Scutellaria baicalensis,86 and Vitis vinifera.51,87
Oral chemotherapy for the treatment of hepatocellular carcinoma
Published in Expert Opinion on Pharmacotherapy, 2018
Brivanib is an oral dual inhibitor of VEGF and fibroblast growth factor (FGF) signaling. The BRISK-FL study that compared brivanib with sorafenib as first-line therapy in patients with advanced HCC was conducted, and the OS (primary endpoint) were 9.5 months in the brivanib arm and 9.9 months in the sorafenib arm. The study did not show the primary endpoint OS non-inferiority for brivanib vs. sorafenib [16]. BRISK-PS study that compared brivanib with placebo as second-line therapy in patients with advanced HCC was also conducted, and the OS (primary endpoint) were 9.4 months in the brivanib arm and 8.2 months in the placebo arm, with no significant difference between the two arms (HR: 1.07, 95% CI: 0.94–1.23, P = 0.312) [17].