Biologic Therapy in Head and Neck Cancer: A Road with Hurdles

Specenier, Pol; Vermorken, Jan B.

doi:10.5402/2012/163752

Cited by 17 publications

(29 citation statements)

References 95 publications

(92 reference statements)

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“…Thus far, cetuximab (Erbitux ® ; Merck KgaA, Darmstadt, Germany; Imclone Systems, Somerville, NJ, USA) is the only targeted agent which has been approved for the treatment of SCCHN by the regulatory agencies of the United States and Europe 16,17. Cetuximab is a chimeric monoclonal antibody of the immunoglobulin G1 class, which binds with high affinity to the extracellular domain of the human EGFR.…”

Section: Review Of Pharmacology Mode Of Action and Pharmacokineticsmentioning

confidence: 99%

Cetuximab: its unique place in head and neck cancer treatment

Specenier¹,

Vermorken²

2013

BTT

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Head and neck cancer is the sixth most common cancer worldwide. At present, globally about 650,000 new cases of squamous cell carcinoma of the head and neck (SCCHN) are diagnosed each year. The epidermal growth factor receptor (EGFR) is almost invariably expressed in SCCHN. Overexpression of the EGFR is a strong and independent unfavorable prognostic factor in SCCHN. Cetuximab is a chimeric monoclonal antibody, which binds with high affinity to the extracellular domain of the human EGFR, blocking ligand binding, resulting in inhibition of the receptor function. It also targets cytotoxic immune effector cells towards EGFR-expressing tumor cells (antibody dependent cell-mediated cytotoxicity). The addition of cetuximab to radiotherapy (RT) improves locoregional control and survival when compared to RT alone. The addition of cetuximab to platinum-based chemoradiation (CRT) is feasible but does not lead to an improved outcome. Cetuximab plus RT has never been compared prospectively to CRT, which therefore remains the standard treatment for patients with locoregionally advanced SCCHN for whom surgery is not considered the optimal treatment, provided they can tolerate CRT. The addition of cetuximab to platinum-based chemotherapy prolongs survival in patients with recurrent or metastatic SCCHN. The combination of a platinum-based regimen and cetuximab should be considered as the standard first line regimen for patients who can tolerate this treatment.

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Section: Review Of Pharmacology Mode Of Action and Pharmacokineticsmentioning

confidence: 99%

Cetuximab: its unique place in head and neck cancer treatment

Specenier¹,

Vermorken²

2013

BTT

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“…A second trial, SPECTRUM (phase III; NCT00460265), compared cisplatin/5-FU plus panitumumab to cisplatin/5-FU alone in patients with metastatic/recurrent SCCHN. The addition of panitumumab to chemotherapy did not significantly improve median overall survival versus chemotherapy alone but did improve median PFS (5.8 vs. 4.6 months) [138].…”

Section: Additional Egfr-targeting Antibodiesmentioning

confidence: 99%

“…4.2). Cetuximab binds to EGFR with a higher affinity than its natural ligands EGF and TGFα [136]- [138]. Once bound to EGFR domain III, cetuximab occludes the ligand-binding site, thus inhibiting ligand-dependent EGFR signaling [139].…”

Section: Cetuximabmentioning

confidence: 99%

“…In 286 patients with metastatic/recurrent SCCHN after failure of platinum-based therapy, zalutumumab plus best supportive care was compared with best supportive care plus methotrexate at the investigator's discretion [152]. Zalutumumab did not increase overall survival, although progression-free survival was extended [138]. A phase III trial is currently underway (DAHANCA 19; NCT00496652) to determine if the addition of zalutumumab to radiotherapy improves locoregional control.…”

Section: Additional Egfr-targeting Antibodiesmentioning

confidence: 99%

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EGFR Inhibitors as Therapeutic Agents in Head and Neck Cancer

Liu

Cracchiolo

Beck

et al. 2014

Molecular Determinants of Head and Neck Cancer

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Squamous cell carcinoma of the head and neck (SCCHN) is one of the more challenging cancers to treat. Although great progress has been made over the years, available treatment options are still far from ideal, as epitomized by a 5-year survival rate of only 30-40 %. A unique feature of SCCHN is that elevated expression of the epidermal growth factor receptor (EGFR), a member of the ErbB receptor tyrosine kinase (RTK) family and highly relevant to oncogenic proliferation, occurs in a significant number of cases, which has prompted great interest in utilizing EGFR-targeted therapies to treat this devastating disease. Significant advances in the treatment of SCCHN have been made using EGFR-targeting monoclonal antibodies. Another class of EGFR-targeting inhibitors, tyrosine kinase inhibitors (TKIs), has also shown promise as a potential treatment option. In order to appreciate how these therapeutic agents work and why they fail when they do, it is crucial to explore the biology of the ErbB family members, the signaling pathways that are associated with them, and how they interact with each specific therapeutic agent. This chapter discusses the biology of EGFR and other ErbB family members in SCCHN, and summarizes the current status of the application of EGFR and ErbB inhibitors.Keywords Epidermal growth factor receptor (EGFR) · Squamous cell carcinoma of the head and neck (SCCHN) · Tyrosine kinase inhibitor (TKI) · Monoclonal antibodies · Erlotinib · Cetuximab · Radiation · Cisplatin · ErbB family

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“…Squamous cell carcinoma of the head and neck (SCCHN) represents approximately 90% of all cancer arising in the head and neck area [1] and represents the sixth most common type of cancer, diagnosed in over 600,000 patients worldwide every year [2]. Prognostic factors in SCCHN are limited, except for the recognized positive role of human papilloma virus (HPV), mainly in association with oropharyngeal cancer.…”

Section: Introductionmentioning

confidence: 99%

Radiotherapy plus EGFR inhibitors: synergistic modalities

Bossi

Platini

2017

Cancers Head Neck

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Locally advanced (stage III or IV) squamous cell carcinoma of the head and neck (SCCHN) often requires multimodal treatment, consisting of a combination of surgery, radiation, and/or systemic therapy, namely chemotherapy or targeted agents. The expression of the epidermal growth factor receptor (EGFR) has been detected in more than 90% of all cases of SCCHN and has been correlated with decreased survival rates, resistance to radiotherapy, loco-regional treatment failure, and increased rates of distant metastases. This paper discusses several strategies aimed at targeting EGFR in combination with radiation. Until now, cetuximab, an anti-EGFR monoclonal antibody, is the only targeted agent that has been shown to improve overall survival in combination with radiation therapy. However, considering that there are multiple mechanisms of primary and acquired resistance to EGFR inhibitors, we focused on dissecting molecular pathways of EGFR inhibition to find alternative or complementary strategies for increasing tumour responsiveness. We suggest that the combination of treatments targeting the EGFR pathway and drugs aimed at increasing immune responses represent a promising approach that deserves to be further explored.

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Biologic Therapy in Head and Neck Cancer: A Road with Hurdles

Cited by 17 publications

References 95 publications

Cetuximab: its unique place in head and neck cancer treatment

Cetuximab: its unique place in head and neck cancer treatment

EGFR Inhibitors as Therapeutic Agents in Head and Neck Cancer

Radiotherapy plus EGFR inhibitors: synergistic modalities

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