Angiogenesis Inhibitors for Head and Neck Squamous Cell Carcinoma Treatment: Is There Still Hope?

Abstract

BackgroundHead and neck squamous cell carcinoma (HNSCC) carries poor survival outcomes despite recent progress in cancer treatment in general. Angiogenesis is crucial for tumour survival and progression. Therefore, several agents targeting the pathways that mediate angiogenesis have been developed. We conducted a systematic review to summarise the current clinical trial data examining angiogenesis inhibitors in HNSCC.MethodsWe carried out a literature search on three angiogenesis inhibitor categories—bevacizumab, tyrosine kinase inhibitors and endostatin—from Ovid MEDLINE, Cochrane Library, Scopus and ClinicalTrials.gov database.ResultsHere, we analysed 38 clinical trials, total of 1670 patients, investigating 12 angiogenesis inhibitors. All trials were in phase I or II, except one study in phase III on bevacizumab. Angiogenesis inhibitors were used as mono- and combination therapies together with radio-, chemo-, targeted- or immunotherapy. Among 12 angiogenesis inhibitors, bevacizumab was the most studied drug, included in 13 trials. Although bevacizumab appeared effective in various combinations, it associated with high toxicity levels. Endostatin and lenvatinib were well-tolerated and their anticancer effects appeared promising.ConclusionsMost studies did not show benefit of angiogenesis inhibitors in HNSCC treatment. Additionally, angiogenesis inhibitors were associated with considerable toxicity. However, some results appear encouraging, suggesting that further investigations of angiogenesis inhibitors, particularly in combination therapies, for HNSCC patients are warranted.Systematic Review RegistrationPROSPERO (https://www.crd.york.ac.uk/prospero/), identifier CRD42020157144.

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“…Cetuximab is an EGFR-targeted monoclonal antibody that improved the OS of HNSCC patients in both locally advanced and recurrent/metastatic settings, which was approved to be used as the standard treatment option in in the USA and Japan ( 8 ). The overexpression of the vascular endothelial growth factor (VEGF) in HNSCC also attracts people’s attention, while most studies did not show clinical benefit of angiogenesis inhibitors such as bevacizumab, tyrosine kinase inhibitors, and endostatin ( 9 ).…”

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“…In a phase-III trial in R/M HNSCC, adding bevacizumab to platinum-based chemotherapy significantly improved both the PFS ( p = 0.0014) and ORR ( p = 0.016), although no significant improvement in OS was found [ 119 ]. Moreover, the bevacizumab-chemotherapy combination was associated with significantly more treatment-related grade 3–5 bleeding events (6.7% vs. 0.5%; p < 0.001) and treatment-related deaths (9.3% vs. 3.2%; p = 0.022) than chemotherapy alone [ 120 ].…”

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“…Angiogenesis is defined as the process of new blood vessel formation, which plays a crucial role in tumor growth, invasion and metastasis 108 . The process of angiogenesis is primarily mediated by the vascular endothelial growth factor (VEGF) pathway 109 . Compared to cytotoxic chemotherapy, angiogenesis is an attractive biological target as the drugs that inhibit angiogenesis should primarily affect the viability of cancer cells 110 .…”

“…108 The process of angiogenesis is primarily mediated by the vascular endothelial growth factor (VEGF) pathway. 109 Compared to cytotoxic chemotherapy, angiogenesis is an attractive biological target as the drugs that inhibit angiogenesis should primarily affect the viability of cancer cells. 110 The United States Food and Drug Administration has approved the use of antiangiogenic drugs, including Avastin, Tarceva, Iressa and Cyramza, for the treatment of colorectal renal cell ovarian cancer, gastric and thyroid cancer (www.fda.gov).…”