Gastric mucosa protection in patients treated with iressa and COX-2 inhibitors in malignancies

Background: Gefitinib (ZD1893, Iressa) is an orally active, selective EGFR tyrosine-kinase inhibitor recently approved for the treatment of non-small cell lung cancer (NSCLC) by the FDA. At present, this drug represents one of the most attractive perspectives for the therapy of advanced stage patients especially with brain metastases, who are not eligible for conventional chemotherapy. Also COX-2 inhibitors have been shown to have inhibitory effect on different types of neoplastic conditions including NSCLC. Drugs that cause significant sustained elevation in gastric pH (>5), may reduce plasma concentrations of gefitinib resulting in reduced efficacy. Therefore, no form of antacids including H2-blockers or PPIs can be recommended.

Our patient: A 63-year-old female patient with primary bronchial adenocarcinoma and brain metastases was approved for Iressa treatment (OGyI). After failure of whole brain irradiation she was put on COX2 inhibitory treatment and has been stable for the past 6 months w/o progression of metastases. In the past, she had gastrointestinal bleeding (1985) due to gastric ulcer and she has been on H2 blockers since ever. At present, she was put on sucralfate between meals in addition to Celecoxib/200mg/ and Iressa/250mg/ at breakfast while the H2 blockers were discontinued.

Discussion: special attention should focus on combined EGFR/COX2 inhibitory therapy on high risk patients for ulcer disease. As for the time being, close monitoring of these patients with regular FOB tests and/or screening endoscopies may be warranted in addition to sucralfate and related drugs enhancing gastric mucosa protection.