Evaluation of the EGFR-Inhibitor Zalutumumab Given With Primary Curative (Chemo)radiation Therapy to Patients With Squamous Cell Carcinoma of the Head and Neck: Results of the DAHANCA 19 Randomized Phase 3 Trial

Eriksen, Jesper Grau; Maare, C.; Johansen, Jørgen; Primdahl, Hanne; Evensen, Jan F.; Kristensen, Claus Andrup; Andersen, Ljubica Vukelic; Overgaard, Jens

doi:10.1016/j.ijrobp.2013.11.021

Cited by 21 publications

(31 citation statements)

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“…Six larger RCTs with more than 100 randomized patients per treatment arm were identified [42, 52, 55, 60, 72, 73]. Bonner et al compared the addition of weekly cetuximab with concomitant boost accelerated, hyperfractionated, or conventionally fractionated RT in 424 patients with LASCCHN.…”

Section: Resultsmentioning

confidence: 99%

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Systemic therapy in the curative treatment of head and neck squamous cell cancer: A systematic review

Winquist

Agbassi

Meyers

et al. 2017

Journal of Otolaryngology - Head & Neck Surgery

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ObjectiveTo review the available evidence and make recommendations regarding use of systemically administered drugs in combination or in sequence with radiation (RT) and/or surgery for cure and/or organ preservation in patients with locally advanced nonmetastatic (Stage III to IVB) squamous cell carcinoma of the head and neck (LASCCHN).MethodRecognizing the Meta-analysis of Chemotherapy in Head and Neck Cancer (MACH-NC) group reports have de facto guided practice since 2000, we searched for systematic reviews in the MEDLINE, EMBASE and Cochrane Database of Systematic Reviews published from January 2000 to February 2015 in reference to 4 research questions. A search was also conducted for randomized trials (RCTs) up to February 2015 not included in the meta-analyses.ResultThe MACH-NC reports, 5 additional meta-analyses, and 30 RCTs not included by MACH-NC were identified. For chemotherapy, MACH-NC findings showing improved overall survival with concomitant chemoRT did not require modification. High-dose cisplatin was most commonly studied. We confirmed this benefit with cisplatin monotherapy in patients treated with with postoperative concurrent chemoRT. Other than cetuximab, no targeted agents and radiosensitizers studied in RCTs were shown effective. TPF induction chemotherapy was superior to PF for tumor response and larynx preservation but not survival. Larynx preservation was reported with both CRT and induction chemotherapy approaches.ConclusionChemoRT with cisplatin at least 40 mg/m2 per week given as radical or postoperative adjuvant remains a standard treatment approach for LASCCHN that improves overall survival but increases toxicity. 5-FU plus platinum is supported by less data but may be a reasonable alternative for patients unsuitable for cisplatin. Of note, stratification of outcomes by HPV-status was not available but outcomes for oropharynx cancer appeared similar to other subsites in chemoRT RCTs. No RCTs have yet demonstrated superiority or non-inferiority of cetuximab-RT to CRT. In view of this, cetuximab-RT is suggested only for patients not candidates for CRT. Taxane-based triplet induction chemotherapy is superior to doublets for rapid tumour downsizing and for larynx preservation, but does not improve overall survival and should be used with primary G-CSF prophylaxis. Further investigation of induction approaches for larynx preservation may be warranted.

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Section: Resultsmentioning

confidence: 99%

“…Three larger RCTs tested the addition of anti-EGFR MoAb to accelerated fraction CRT [55, 72, 73]. Ang et al investigated the addition of cetuximab to concomitant boost accelerated RT plus high-dose cisplatin (two cycles) in 891 randomized patients.…”

Section: Resultsmentioning

confidence: 99%

Systemic therapy in the curative treatment of head and neck squamous cell cancer: A systematic review

Winquist

Agbassi

Meyers

et al. 2017

Journal of Otolaryngology - Head & Neck Surgery

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“…However, cisplatin might not be the most optimal cytotoxic radiosensitizing agent when EGFR inhibitor is added to concurrent CRT. In addition to the RTOG 0522 trial mentioned above, Eriksen et al recently reported a Danish randomized study (DAHANCA 19) showing that the addition of zalutumumab, a monoclonal antibody to EGFR receptor, to cisplatin‐radiotherapy and nimorazole did not increase the locoregional control, DFS, or OS at 3 years. Mesia et al also reported that the addition of panitumumab, a fully human monoclonal antibody targeting EGFR, to standard fractionation radiotherapy and cisplatin did not confer any benefit in patients with locally advanced HNSCC.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, recent data have emerged that the addition of EGFR inhibitors to concurrent cisplatin CRT did not improve treatment outcomes, possibly because of the similar effects on DNA repair by these agents. [12][13][14][15] Therefore, chemotherapeutic agents other than cisplatin should be evaluated in combination with EGFR inhibitors and radiotherapy.…”

Section: Introductionmentioning

confidence: 99%

Phase II study of erlotinib and docetaxel with concurrent intensity‐modulated radiotherapy in locally advanced head and neck squamous cell carcinoma

Yao

Woods

et al. 2016

Head & Neck

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Background To establish the efficacy and toxicities of concurrent erlotinib and docetaxel with IMRT for locally advanced head and neck squamous cell carcinoma (HNSCC). Methods Patients received daily erlotinib for two weeks, followed by daily IMRT with concurrent weekly docetaxel and daily erlotinib, followed by daily erlotinib for up to two years. The primary objective was disease-free survival (DFS). Secondary objectives included overall survival (OS), patterns of failure, and toxicities. Forty-three patients were recruited. Results With a median follow-up of 48.7 months, the 3 year DFS, OS, locoregional failure free survival and distant metastasis free survival was 69.5%, 81%, 82.4%, and 83.7%, respectively. The most common grade III/IV local toxicities were dysphagia, dermatitis and mucositis. Patients with P16+ tumor had significantly better outcomes. Conclusions The regimen is tolerable and effective. It is worthy of further investigation in selected patients and may be useful in patients who cannot tolerate cisplatin.

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“…Cetuximab (Erbitux®) is approved for treatment of colorectal and head-and-neck cancers, and panitumumab (Vectabix®) is approved for treatment of colorectal cancers [ 22 ]. However, newer therapeutics like matuzumab, nimotuzumab, or zalutumumab have shown less promise in clinical trials, and development of several next-generation examples has been discontinued due to little improvement in patient outcomes or adverse patient health effects [ 23 , 24 , 25 , 26 ]. Additional ligand-neutralizing antibodies targeting TGFα or HB-EGF have demonstrated anti-proliferative activity in vitro and inhibition of tumor growth and high dose-tolerability in vivo [ 27 , 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

Immunotoxin Therapies for the Treatment of Epidermal Growth Factor Receptor-Dependent Cancers

Simon

FitzGerald

2016

Toxins

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Many epithelial cancers rely on enhanced expression of the epidermal growth factor receptor (EGFR) to drive proliferation and survival pathways. Development of therapeutics to target EGFR signaling has been of high importance, and multiple examples have been approved for human use. However, many of the current small molecule or antibody-based therapeutics are of limited effectiveness due to the inevitable development of resistance and toxicity to normal tissues. Recombinant immunotoxins are therapeutic molecules consisting of an antibody or receptor ligand joined to a protein cytotoxin, combining the specific targeting of a cancer-expressed receptor with the potent cell killing of cytotoxic enzymes. Over the decades, many bacterial- or plant-based immunotoxins have been developed with the goal of targeting the broad range of cancers reliant upon EGFR overexpression. Many examples demonstrate excellent anti-cancer properties in preclinical development, and several EGFR-targeted immunotoxins have progressed to human trials. This review summarizes much of the past and current work in the development of immunotoxins for targeting EGFR-driven cancers.

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Evaluation of the EGFR-Inhibitor Zalutumumab Given With Primary Curative (Chemo)radiation Therapy to Patients With Squamous Cell Carcinoma of the Head and Neck: Results of the DAHANCA 19 Randomized Phase 3 Trial

Cited by 21 publications

References 0 publications

Systemic therapy in the curative treatment of head and neck squamous cell cancer: A systematic review

Systemic therapy in the curative treatment of head and neck squamous cell cancer: A systematic review

Phase II study of erlotinib and docetaxel with concurrent intensity‐modulated radiotherapy in locally advanced head and neck squamous cell carcinoma

Immunotoxin Therapies for the Treatment of Epidermal Growth Factor Receptor-Dependent Cancers

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