P001 Phase 1 Study of Erlotinib, Docetaxel, and Radiation in Locally Advanced Squamous Cell Cancer of the Head and Neck

Savvides, P.; Agarwala, Sanjiv S.; Greskovich, J.F.; Argiris, Athanassios; Bokar, Joseph A.; Pagedar, Nitin A.; Hoppel, Charles L.; Stepnick, David W.; Remick, S. C.

doi:10.1001/archotol.132.8.865-a

Cited by 9 publications

(11 citation statements)

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“…with induction chemotherapy (docetaxel/5-FU/carboplatin) in locally advanced SCCHN demonstrated that this regimen was feasible and produced high RR (11 CRs, 18 PRs, five SDs out of 34 patients) (Doss et al, 2006). Two phase I/II studies of erlotinib in combination with docetaxel or cisplatin and radiotherapy in locally advanced SCCHN demonstrated that these combinations are safe and feasible (Herchenhorn et al, 2006;Savvides et al, 2006). Phase II trials are planned or ongoing (Table 4).…”

Section: Tkis In Combination With Radiotherapymentioning

confidence: 99%

Targeting EGF-receptor-signalling in squamous cell carcinomas of the head and neck

2007

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Despite significant advances in the use of surgery, chemotherapy and radiotherapy to treat squamous cell carcinoma of the head and neck (SCCHN), prognosis has improved little over the past 30 years. There is a clear need for novel, more effective therapies to prevent relapse, control metastases and improve overall survival. Improved understanding of SCCHN disease biology has led to the introduction of molecularly targeted treatment strategies in these cancers. The epidermal growth factor receptor (EGFR) is expressed at much higher levels in SCCHN tumours than in normal epithelial tissue, and EGFR expression correlates with poor prognosis. Therefore, much effort is currently directed toward targeting aberrant EGFR activity (e.g. cell signalling) in SCCHN. This review discusses the efficacy of novel therapies targeting the EGFR (e.g. anti-EGFR antibodies and EGFR tyrosine kinase inhibitors) that are currently tested in SCCHN patients.

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Section: Tkis In Combination With Radiotherapymentioning

confidence: 99%

Targeting EGF-receptor-signalling in squamous cell carcinomas of the head and neck

2007

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“…Type 1 TKIs, such as erlotinib (OSI-774) and gefi tinib (ZD1839), target the ATP binding site of the kinase domain in its active conformation. Erlotinib and gefi tinib are being used with various radiochemotherapy regimens [97][98][99][100][101] (Table 1). Like erlotinib and gefi tinib, CI-1033 is an orally active lowmolecular-weight inhibitor of tyrosine kinase.…”

Section: Resistance To Egfr Inhibitorsmentioning

confidence: 99%

Combination of radiotherapy with EGFR antagonists for head and neck carcinoma

et al. 2007

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The introduction of biologically sound radiation fractionation regimens and combinations of radiotherapy with chemotherapy have gradually improved both the survival of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) and the prospect of organ preservation. Long-term follow-up, however, has shown that some of the radiation-chemotherapy combinations are associated with increased late toxicity. This observation, in conjunction with advances in tumor biology, has led to the launch of investigations into molecular markers and targets for therapeutic interventions. Research on the epidermal growth factor receptor (EGFR)-mediated signaling pathway has enriched our understanding of the biology of HNSCC, in terms of carcinogenesis and cellular processes governing tumor response to therapy. The finding that the addition of an antibody-based inhibitor of the EGFR pathway to radiotherapy significantly improves locoregional control and overall survival rates in patients with locally advanced HNSCC, without increasing radiation-induced toxicity, has resulted in the growing acceptance of such combined regimens as a frontline therapy option for locally advanced HNSCC. Because such therapy has benefited only an additional 10%-15% of patients, studies are being undertaken to identify markers and mechanisms of resistance to EGFR antagonists that are essential for the further refinement of therapy. Overall, preclinical and clinical studies on EGFR have validated the concept that selective tumor radiation sensitization can be achieved by modulating a specific perturbed signaling pathway, and these studies have increased the enthusiasm for developing and investigating other novel agents targeting other cellular processes.

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“…In a phase I trial Savvides et al combined erlotinib with docetaxel and RT in locally advanced HNSCC (Savvides et al, 2006). The regimen consisted of weekly docetaxel (15 to 20 mg/m2) plus daily erlotinib (50 to 150 mg) with concurrent RT (70 Gy) followed by maintenance erlotinib for up to 2 years.…”

Section: Erlotinibmentioning

confidence: 99%

Novel Chemoradiotherapy Regimens Incorporating Targeted Therapies in Locally Advanced Head and Neck Cancers

Rathore¹

2012

Head and Neck Cancer

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A forest plot analysis was done to assess whether certain patient groups benefitted with the addition of cetuximab to RT. In this analysis, factors which were associated with a potential increased benefit included presence of oropharyngeal tumors, concomitant boost RT, early T stage (T1-T3), high Karnofsky performance score (90%-100%), male sex, and age < 65 years. These results are provocative but given that the trial was not powered for this subgroup analysis, they should be interpreted with caution.Patients who received cetuximab commonly developed an acneiform rash (83.7%); the severity of the rash was grade 3-4 in 16.8% patients. Infusion-related reactions were also seen in 15.4% patients; in 3.9% patients these were of grade 3/4 severity. However, in-field toxicities, such as mucositis, dermatitis, and dysphagia did not significantly increase with the addition of cetuximab to RT. Quality-of-life parameters were not adversely affected by the addition of cetuximab. This study allowed different RT fractionation regimens which may have impacted results and survival outcomes.

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P001 Phase 1 Study of Erlotinib, Docetaxel, and Radiation in Locally Advanced Squamous Cell Cancer of the Head and Neck

Cited by 9 publications

References 0 publications

Targeting EGF-receptor-signalling in squamous cell carcinomas of the head and neck

Targeting EGF-receptor-signalling in squamous cell carcinomas of the head and neck

Combination of radiotherapy with EGFR antagonists for head and neck carcinoma

Novel Chemoradiotherapy Regimens Incorporating Targeted Therapies in Locally Advanced Head and Neck Cancers

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