Dataset Information

Cetuximab activity in dysplastic lesions of the upper aerodigestive tract.

ABSTRACT:

Background

High risk head and neck mucosal premalignancy has a malignant conversion rate of up to 40%, despite adequate surgical therapy. Epidermal Growth Factor Receptor (EGFR) blocking agents, including cetuximab, have shown activity in head and neck squamous cell carcinoma (HNSCC) and have potential for therapy in high risk premalignancy.

Methods

We conducted a randomized, prospective, phase II clinical trial to determine the effects of cetuximab on patients with high risk premalignancy. Patients were randomized to treatment with cetuximab 400mg/m(2) on week one followed by 250mg/m(2) on week 2-8 or observation, with the option for crossover to cetuximab therapy for patients originally randomized to the observation arm.

Results

Two of 19 enrolled patients did not complete therapy due to treatment toxicity. Analysis of 17 patients who completed the trial regimen show a trend toward a larger mean decrease in grade of dysplasia in the cetuximab treated group (-1.0) vs. the observation group (-0.2) (P=0.082, one-sided exact Wilcoxon rank sum test). However, in the observation group, none of the 5 patients (0%) achieved complete resolution of dysplasia; while 4 of 12 (33.3%) cetuximab treated patients had no remaining dysplasia after therapy.

Conclusions

Treatment of high risk premalignancy of the upper aerodigestive tract with cetuximab alone may result in significant, durable, and complete clinical and histological resolution of moderate to severe dysplasia in at least a subset of high risk patients. These results warrant further investigation in larger studies with increased statistical power.

SUBMITTER: Khan Z

PROVIDER: S-EPMC7751887 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Publications

Cetuximab activity in dysplastic lesions of the upper aerodigestive tract.

Khan Zubair Z Epstein Joel B JB Marur Shanthi S Gillespie M Boyd MB Feldman Lawrence L Tsai Hua-Ling HL Zhang Zhe Z Wang Hao H Sciubba James J Ferris Robert R Grandis Jennifer R JR Gibson Michael M Koch Wayne W Tufano Ralph R Westra William W Tsottles Nancy N Ozawa Hiroyuki H Chung Christine C Califano Joseph A JA

Oral oncology 20151210

<h4>Background</h4>High risk head and neck mucosal premalignancy has a malignant conversion rate of up to 40%, despite adequate surgical therapy. Epidermal Growth Factor Receptor (EGFR) blocking agents, including cetuximab, have shown activity in head and neck squamous cell carcinoma (HNSCC) and have potential for therapy in high risk premalignancy.<h4>Methods</h4>We conducted a randomized, prospective, phase II clinical trial to determine the effects of cetuximab on patients with high risk prem ...[more]

PMID: 26686755

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Project description:BACKGROUND: EPHX1 is a key enzyme in metabolizing some exogenous carcinogens such as products of cigarette-smoking. Two functional polymorphisms in the EPHX1 gene, Tyr113His and His139Arg can alter the enzyme activity, suggesting their possible association with carcinogenesis risk, particularly of some tobacco-related cancers. METHODOLOGY/PRINCIPAL FINDINGS: A comprehensive systematic review and meta-analysis was performed of available studies on these two polymorphisms and cancer risk published up to November 2010, consisting of 84 studies (31144 cases and 42439 controls) for Tyr113His and 77 studies (28496 cases and 38506 controls) for His139Arg primarily focused on lung cancer, upper aerodigestive tract (UADT) cancers (including oral, pharynx, larynx and esophagus cancers), colorectal cancer or adenoma, bladder cancer and breast cancer. Results showed that Y113H low activity allele (H) was significantly associated with decreased risk of lung cancer (OR = 0.88, 95%CI = 0.80-0.96) and UADT cancers (OR = 0.86, 95%CI = 0.77-0.97) and H139R high activity allele (R) with increased risk of lung cancer (OR = 1.18, 95%CI = 1.04-1.33) but not of UADT cancers (OR = 1.05, 95%CI = 0.93-1.17). Pooled analysis of lung and UADT cancers revealed that low EPHX1 enzyme activity, predicted by the combination of Y113H and H139R showed decreased risk of these cancers (OR = 0.83, 95%CI = 0.75-0.93) whereas high EPHX1 activity increased risk of the cancers (OR = 1.20, 95%CI = 0.98-1.46). Furthermore, modest difference for the risk of lung and UADT cancers was found between cigarette smokers and nonsmokers both in single SNP analyses (low activity allele H: OR = 0.77/0.85 for smokers/nonsmokers; high activity allele R: OR = 1.20/1.09 for smokers/nonsmokers) and in combined double SNP analyses (putative low activity: OR = 0.73/0.88 for smokers/nonsmokers; putative high activity: OR = 1.02/0.93 for smokers/ nonsmokers). CONCLUSIONS/SIGNIFICANCE: Putative low EPHX1 enzyme activity may have a potential protective effect on tobacco-related carcinogenesis of lung and UADT cancers, whereas putative high EPHX1 activity may have a harmful effect. Moreover, cigarette-smoking status may influence the association of EPHX1 enzyme activity and the related cancer risk.

Dataset Information

Cetuximab activity in dysplastic lesions of the upper aerodigestive tract.

Background

Methods

Results

Conclusions

Publications

Cetuximab activity in dysplastic lesions of the upper aerodigestive tract.

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