Source: Nature Reviews Clinical Oncology 6, 302 (June 2009)
Author: Mandy Aujla

Researchers have developed an antisense EGFR sequence to target EGFR, and found that this approach was safe and effective in patients with advanced squamous-cell carcinoma of the head and neck.

Standard treatment for this type of cancer is suboptimal. Various drugs have been developed to block this increased signaling, such as cetuximab and erlotinib. These agents, however, have had limited success when used as monotherapy in treating squamous-cell carcinoma of the head and neck. Despite encouraging preclinical data these agents produce low response rates and are associated with toxic effects. Therefore, alternative approaches that target EGFR are needed. In this phase I trial, Lai and colleagues evaluated the safety and toxicity of EGFR antisense DNA therapy in 20 patients with advanced squamous-cell carcinoma of the head and neck. All patients included in the study had advanced disease that was unresponsive to standard therapies.

The researchers tested six levels of the antisense EGFR at doses ranging from 60 to 1,920 g per injection, with three patients in each dose tier. The antisense EGFR was injected into the most accessible single tumor lesion once a week for 4 weeks. A biopsy was performed within 2 weeks of the final injection.

A total of 17 patients completed the treatment course and were available for assessment. Of the five patients who achieved a clinical response, two had a complete response and three achieved a partial response. Two other patients had stable disease. A maximum-tolerated dose was not reached and there were no grade 3 or 4 dose-limiting toxic effects.

Direct injection of an antisense EGFR sequence into tumors might be a promising treatment approach for head and neck cancer.

Note:
1. Original article Lai, S. Y. et al. Intratumoral epidermal growth factor receptor antisense DNA therapy in head and neck cancer: first human application and potential antitumor mechanisms. J. Clin. Oncol. 27, 1235–1242 (2009). PubMed