Genta cancer drug increases Iressa activity

Gefitinib (marketed as Iressa by AstraZeneca) has been recently approved for clinical treatment of patients with advanced non-small cell lung cancer (NSCLC) and is an inhibitor of epidermal growth factor receptor tyrosine kinase (EGFR-TK).

Recent studies have suggested that clinical response to gefitinib is highly dependent upon the presence of specific mutations in the EGFR gene, which are found in only a small subset of patients with NSCLC. The present study was undertaken to evaluate whether Genasense (oblimersen sodium injection) could enhance the anticancer response to gefitinib, and also to evaluate whether Genasense could overcome the limitations to gefitinib activity that may be dependent upon EGFR mutations.

Using experimental xenograft models of human NSCLC cells, Genasense used alone showed somewhat greater inhibition of tumor growth in mice compared with single-agent gefitinib. However, the combination of both drugs yielded considerably enhanced anti-tumor activity.

Finally, preliminary data using both erlotinib (OSI Pharmaceuticals and Genentech’s Tarceva) and permetrexed (Eli Lilly’s Alimta) – an EGFR inhibitor and antifol, respectively, that were recently approved for marketing in NSCLC – have revealed similar results in combination with Genasense in these models.

“These studies extend the synergistic potential of Genasense into a new class of anticancer compounds, the EGFR-tyrosine kinase inhibitors,” said Dr Bob Brown, Genta’s vice-president of research and technology. “The only prior study using a tyrosine kinase inhibitor showed that Genasense could enhance the anti-leukemic activity of imatinib (Novartis’ Gleevec) in a model of chronic myelocytic leukemia (CML), and this combination is now being evaluated in a clinical trial.”