NEW YORK (Reuters Health) – In a phase I trial involving patients with advanced squamous cell carcinoma of the head and neck (SCCHN), direct intratumoral injection of epithelial growth factor receptor antisense (EGFR AS) DNA was safe and nontoxic and demonstrated antitumor activity, investigators report.

Although SCCHN is characterized by upregulation of EGFR, treatment with monoclonal antibodies or tyrosine kinase inhibitors targeting the receptor has had little effect, the authors explain in the Journal of Clinical Oncology, posted online on February 9.

The trial, headed by Dr. Jennifer R. Grandis at the University of Pittsburgh, involved 20 patients with advanced SCCHN disease refractory to standard therapies who had at least one evaluable accessible lesion. The EGFR AS plasmid DNA dose was escalated in successive cohorts (range 60-1920 µg), administered in 4 weekly injections.

Three patients died before their tumors could be assessed or before completing all 4 injections. In the remaining 17, the disease control rate was 41% (2 complete responders, 3 partial responders, and 2 patients with stable disease), with overall median duration of response or time to progression at the target lesion of 1.4 months. In the 7 patients with disease control, median time to progression was 6.5 months (maximum 23 months).

Among the 8 patients with assessable specimen pairs, EGFR expression decreased during treatment in 7, the researchers report. The degree of EGFR downregulation was most pronounced in tumors that responded to treatment.

There were no grade 3 or 4 toxicities, and the maximum-tolerated dose was not reached, the report indicates.

Based on biopsies obtained prior to treatment, Dr. Grandis’ team found that treatment response was associated with higher EGFR expression and lower baseline STAT3 levels.

They propose that “downregulating EGFR may be most effective in those tumors with high EGFR levels in which these cells are unable to compensate through other oncogenic signaling pathways, such as STAT3.”

Reference:
J Clin Oncol 2009.