Phase I Trial Using Induction Ciplatin, Docetaxel, 5-FU and Erlotinib Followed by Cisplatin, Bevacizumab and Erlotinib With Concurrent Radiotherapy for Advanced Head and Neck Cancer

Ahn, Peter H.; Machtay, Mitchell; Anné, Pramila R.; Cognetti, David M.; Keane, William M.; Wuthrick, Evan; Dicker, Adam P.; Axelrod, Rita

doi:10.1097/coc.0000000000000317

Cited by 12 publications

(9 citation statements)

References 31 publications

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“…Four trials, three as first-line treatment, combined bevacizumab and epidermal growth factor TKI erlotinib with different types of chemotherapy or chemoradiotherapy. The combination of bevacizumab, erlotinib and chemoradiotherapy (cisplatin, docetaxel and 5-fluorouracil) was active, but toxic ( 16 ). In this phase I study, gastrointestinal toxicities caused high rates of patient withdrawal and the combination was not recommended to advance to phase II ( 16 ).…”

Section: Resultsmentioning

confidence: 99%

“…In some trials, significant toxicities were reported (16,17,26), although in other studies, the same combinations appeared well-tolerated with encouraging results (11,18,19,(21)(22)(23)(24)(25)27). Three categories of combinations were used in the trials: (1) bevacizumab in combination with erlotinib and chemotherapy/ chemoradiotherapy (16,23,27); (2) bevacizumab in combination with cetuximab and chemotherapy/chemoradiotherapy (17,18,21) and ( 3) bevacizumab in combination with chemotherapy or chemoradiotherapy (11,19,20,22,24,26). Significant toxicities, such as a perforation, fistula, diarrhoea, mucositis, dysphagia, haemorrhage and hematologic toxicity, were reported in one trial from all of these treatment combinations, and no further trials were recommended (16,17,26).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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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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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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“…Nevertheless, some combinations, e.g. with induction chemotherapy [90], proved to be extremely toxic or not effective [91] and one of the few randomized trials testing erlotinib in the definitive, curative treatment, failed to show any benefit when compared to standard CRT [92]. Gefitinib was tested in large, phase III randomized trials either as monotherapy compared to methotrexate [93] or as doublet together with docetaxel versus docetaxel plus placebo [94], with both studies revealing negative results.…”

Section: Targeted Therapies For Scchnmentioning

confidence: 99%

“…It is still not clear, if bevacizumab monotherapy is effective in the management of advanced or metastasized SCCHN and some authors report on enhanced toxicity after combination regimens with this agent: in a phase I trial evaluating the combination of bevacizumab with cisplatin, erlotinib and radiation, severe toxicity resulted in a study withdrawal [90] and the agent also seemed to enhance toxicity both in a phase II study investigating a non-platinum-based combination [125] and the rates of osteoradionecrosis in another publication [126]. Also, trials investigating the implementation of bevacizumab-combination regimens for recurrent and poor-prognosis SCCHN showed considerable and often unexpected toxicity [127].…”

Section: Targeted Therapies For Scchnmentioning

confidence: 99%

Targeted Therapies and Immune-Checkpoint Inhibition in Head and Neck Squamous Cell Carcinoma: Where Do We Stand Today and Where to Go?

Grün

Rödel

Brandts

et al. 2019

Cancers

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With an increased understanding of the tumor biology of squamous cell carcinoma of the head and neck (SCCHN), targeted therapies have found their way into the clinical treatment routines against this entity. Nevertheless, to date platinum-based cytostatic agents remain the first line choice and targeting the epidermal growth factor-receptor (EGFR) with combined cetuximab and radiation therapy remains the only targeted therapy approved in the curative setting. Investigation of immune checkpoint inhibitors (ICI), such as antibodies targeting programmed cell death protein 1 (PD-1) and its ligand PD-L1, resulted in a change of paradigms in oncology and in the first approval of new drugs for treating SCCHN. Nivolumab and pembrolizumab, two anti-PD-1 antibodies, were the first agents shown to improve overall survival for patients with metastatic/recurrent tumors in recent years. Currently, several clinical trials investigate the role of ICI in different therapeutic settings. A robust set of biomarkers will be an inevitable tool for future individualized treatment approaches including radiation dose de-escalation and escalation strategies. This review aims to summarize achieved goals, the current status and future perspectives regarding targeted therapies and ICI in the management of SCCHN.

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“…Mounting evidence has demonstrated that molecular markers hold a promising function not only because of their prognostic value but also because of their role as molecular targets. For example, HNSCC therapy has undergone a significant change in recent years with the development of precision medicines, such as bevacizumab, against vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) based on the special gene expression signature, and prognostic outcomes in HNSCC (3)(4)(5). More recently, increasing knowledge has brought into focus the features of several macromolecules (protein, RNA, DNA, and sugar) that are involved in tumorigenesis and progression, especially in epigenetic modifications; and the value of these features as prognostic indicators and potential therapeutic targets has been gradually recognized (6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Identification of Expression Patterns and Potential Prognostic Significance of m5C-Related Regulators in Head and Neck Squamous Cell Carcinoma

et al. 2021

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5-Methylcytosine (m5C) methylation is a major epigenetic technique of RNA modification and is dynamically mediated by m5C “writers,” “erasers,” and “readers.” m5C RNA modification and its regulators are implicated in the onset and development of many tumors, but their roles in head and neck squamous cell carcinoma (HNSCC) have not yet been completely elucidated. In this study, we examined expression patterns of core m5C regulators in the publicly available HNSCC cohort via bioinformatic methods. The differentially expressed m5C regulators could divide the HNSCC cohort into four subgroups with distinct prognostic characteristics. Furthermore, a three-gene expression signature model, comprised of NSUN5, DNMT1, and DNMT3A, was established to identify individuals with a high or low risk of HNSCC. To explore the underlying mechanism in the prognosis of HNSCC, screening of differentially expressed genes, followed by the analysis of functional and pathway enrichment, from individuals with high- or low-risk HNSCC was performed. The results revealed a critical role for m5C RNA modification in two aspects of HNSCC: (1) dynamic m5C modification contributes to the regulation of HNSCC progression and (2) expression patterns of NSUN5, DNMT1, and DNMT3A help to predict the prognosis of HNSCC.

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Phase I Trial Using Induction Ciplatin, Docetaxel, 5-FU and Erlotinib Followed by Cisplatin, Bevacizumab and Erlotinib With Concurrent Radiotherapy for Advanced Head and Neck Cancer

Cited by 12 publications

References 31 publications

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

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

Targeted Therapies and Immune-Checkpoint Inhibition in Head and Neck Squamous Cell Carcinoma: Where Do We Stand Today and Where to Go?

Identification of Expression Patterns and Potential Prognostic Significance of m5C-Related Regulators in Head and Neck Squamous Cell Carcinoma

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