Current Insights and Progress in the Clinical Management of Head and Neck Cancer (original) (raw)
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Emerging patient-specific treatment modalities in head and neck cancer – a systematic review
Expert Opinion on Investigational Drugs, 2019
Introduction: Head and neck cancer (HNC) is an immunosuppressive disease that demonstrates heterogeneous molecular characteristics and features of tumor-host interaction. Beside radiotherapy and surgery, the current standard of care in systemic treatment involves the use of cytotoxic chemotherapy, monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs). There are also other modalities being developed under the category of immunotherapy, but they are overshadowed by the recent advancements of immune checkpoint inhibitors. Areas Covered: This systematic review covers recent advancements in "patient-specific" treatment modalities, which can be only administered to a given patient. Expert Opinion: Currently, patient-specific treatment modalities in HNC mainly consist of active immunotherapy using adoptive cell therapies and/or gene engineered vectors. Despite the slow pace of development, the interest continues in these treatment modalities. The future of HNC treatment is expected to be guided by biomarkers and personalized approaches with tailored combinations of local treatments (radiotherapy, surgery), systemic agents and immune system modulation. Systematic research is required to generate robust data and obtain a high-level of evidence for the effectiveness of such treatment modalities. A c c e p t e d M a n u s c r i p t Article Highlights • HNC is caused by exposure to carcinogenic substances (tobacco, alcohol, industrial chemicals) or oncogenic viruses (HPV, EBV) with distinct pathophysiology, biologic and immune profiles. • The head and neck squamous-cell carcinoma tumor microenvironment is strongly immunosuppressive • Currently, all patient-specific treatment modalities in HNC are under development and mainly consist of active immunotherapy using adoptive cell therapies and/or gene engineered vectors. • Despite of the emergence of advanced techniques, the current data suggest, that it is unlikely to find the ultimate cure for HNC using off-the-shelf or patient-specific immunotherapy in the coming years. • The future of HNC treatment is expected to be guided by biomarkers and personalized with tailored combinations of local treatments (radiotherapy, surgery), systemic agents, and modulation of patients' immune system. • An ideal personalized and patient-specific treatment with 100% on-target action, efficacy and reproducibility, but 0% off-target action and toxicity is not expected in the near future.
Oncology, 2014
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cause of cancer death worldwide. Its treatment is complex and evolving. In general, early-stage disease may be managed with single-modality treatment while an advanced stage (about 60% of clinical presentation) needs a multidisciplinary approach. In this setting concurrent chemoradiation has been associated with improvement in locoregional control and organ preservation, but at the cost of significant acute and chronic toxicity. Molecular target therapies specially directed to epidermal growth factor receptor (EGFR) might improve the outcomes and reduce toxicities. In recurrent-metastatic (R/M) HNSCC, cetuximab, a monoclonal antibody against EGFR, plus platinum-based chemotherapy (CT) allow an overall survival (OS) of about 10 months. However, the prognosis for R/M-HNSCC remains dismal and additional efforts are needed. At the 2013 American Society of Clinical Oncology (ASCO) Meeting, data on induction CT, anti-E...
Targeted therapy in head and neck cancer
Cancer, 2008
In patients with squamous cell carcinoma of the head and neck (SCCHN), tumor recurrence, secondary tumors, and comorbidities contribute to therapy failure, and treatment approaches often are limited by their toxicity. With the incorporation of targeted therapies, the number of options available for patients with SCCHN is growing. The epidermal growth factor receptor (EGFR) is involved in the development and progression of SCCHN and is associated with a poor prognosis. The anti‐EGFR monoclonal antibody (MoAb) cetuximab is the first targeted therapy to be developed for SCCHN. Recent data confirmed a survival advantage and enhanced locoregional control of SCCHN with cetuximab plus radiotherapy (RT) in patients with locally advanced (LA) SCCHN. Single‐agent cetuximab conferred clinical benefits for patients with platinum‐refractory metastatic disease, and a recent phase 3 trial demonstrated a survival benefit with cetuximab and standard platinum‐based therapy in the front‐line treatment...
Current aspects of targeted therapy in head and neck tumors
European Archives of Oto-Rhino-Laryngology, 2008
This review focuses on the current and upcoming options of targeted therapy (biologicals) in head and neck squamous cell carcinoma (HNSCC) with special regard to conceptual integration in future strategies. Epidermal growth factor receptor (EGFR) is the most prominent candidate for therapeutic targeting because of its more than 90% expression rate in HNSCC and inXuence on the regulation of proliferation, apoptosis, metastasis, angiogenesis and cell diVerentiation. The point of view of head and neck surgeons is mainly adjusted to reach a balance between targeted, minimal ablative surgery and the evidence-based demand of oncologic accurate surgery with clear margins and, if needed, adjuvant or primary systemic chemoradiation. Therefore, the long-term eVects of chemoradiation regimens, such as dysphagia, aspiration and laryngeal immobility caused by Wbrosis, are just beginning to be studied and are becoming one of the major problems in the ongoing treatment of HNSCC. In this context, molecular targeting biologicals with a diVerent toxicity proWle and hopefully less late damage to functionally important tissues may open new strategies in primary and adjuvant treatment of HNSCC. Besides cetuximab and other EGFR targeting mAbs, this review focuses on receptor and non-receptor tyrosine kinase inhibitors, which further might play a role in the future treatment of HNSCC. To complete the current picture, the problem of multi drug resistance in cancer progenitor cells, targeting members of several relevant pathways and novel agents like pemetrexed and enzastaurin, are discussed in a broader sense of targeted therapy.
Biologic therapy in head and neck cancer: a road with hurdles
ISRN oncology, 2012
The epidermal growth factor receptor (EGFR) is overexpressed in the vast majority of cases of squamous cell carcinoma of the head and neck (SCCHN). A high EGFR expression is associated with an unfavorable prognosis. Cetuximab is a chimeric human/murine IgG1 antibody which binds with high affinity to the EGFR. It is the only targeted agent which got approval for the treatment of SCCHN from the regulatory agencies of Europe and the United States, both in locoregionally advanced disease, in association with radiation, and in recurrent/metastatic disease. The outcome of trials involving other EGFR-directed monoclonal antibodies, that is, zalutumumab and panitumumab, was consistent with the results with cetuximab. However these trials failed to meet their primary endpoint. The results with EGFR-directed tyrosine kinase inhibitors have been disappointing. Other potential targets for treatment in SCCHN include the entire ErbB family, the vascular endothelial growth factor (VEGF) and its re...
Swiss medical weekly, 2018
Head and neck squamous cell carcinoma (HNSCC) is a frequent tumour arising from multiple anatomical subsites in the head and neck region. The treatment for early-stage disease is generally single modality, either surgery or radiotherapy. The treatment for locally advanced tumours is multimodal. For recurrent/metastatic HNSCC palliative chemotherapy is standard of care. The prognosis is limited and novel treatment approaches are urgently needed. HNSCC evades immune responses through multiple resistance mechanisms. HNSCC is particularly characterised by an immunosuppressive environment which includes the release of immunosuppressive factors, activation, expansion of immune cells with inhibitory activity and decreased tumour immunogenicity. An in-depth understanding of these mechanisms led to rational design of immunotherapeutic approaches and clinical trials. Currently, only immune checkpoint inhibitors, namely monoclonal antibodies targeting the immune inhibitory receptor programmed ...
Optimizing treatments for recurrent or metastatic head and neck squamous cell carcinoma
Expert Review of Anticancer Therapy, 2018
Introduction: The majority of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) will recur. The treatment of patients with recurrent/metastatic (R/M) HNSCC) is rapidly evolving. Areas covered: This article will comprehensively review the current systemic treatment of R/M HNSCC. Expert Commentary: For the time being, the EXTREME regimen (cetuximab in combination with platinum and 5-fluorouracil) still remains standard of care in previously untreated R/M HNSCC patients who are candidates for combination chemotherapy. Single agents with well documented activity in HNSCC include methotrexate, cisplatin, 5-FU, docetaxel, and paclitaxel. The anti-PD-1 monoclonal antibody nivolumab can be considered the current standard of care in patients with R/M HNSCC progressing after platinum-based therapy based on the results of CheckMate 141 showing a survival benefit over standard of care drugs, such as single agent weekly cetuximab, methotrexate, or docetaxel. Multiple randomized phase III trials comparing anti-PD(L)-antibodies either as single agent or in combination with chemotherapy or an anti-CTLA-4 with the EXTREME as fist line treatment are ongoing or planned. The outcome of these trials might change the current treatment paradigm in previously untreated R/M HNSCC. Immunotherapeutic agents under active investigation include Toll-like receptor 8 agonists and inhibitors of IDO1.