SAN ANTONIO—In the first phase II trial of gefitinib(Drug information on gefitinib) (Iressa, also known as ZD1839) in breast cancer, the agent showed limited activity in patients with heavily pretreated metastatic breast cancer, according to a report presented at the 25th Annual San Antonio Breast Cancer Symposium (abstract 20).
But the novel epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor appeared to have some benefit in a subset of patients, and it provided significant relief of bone pain in additional patients, according to Kathy S. Albain, MD, professor of medicine, Division of Hematology/Oncology, Loyola University Health System.
Describing the rationale for using gefitinib in breast cancer, Dr. Albain noted that activation of the EGFR pathway occurs via multiple mechanisms that result in phosphorylation of its intracellular tyrosine kinase domain. This triggers the downstream signaling mediators that lead to breast cancer proliferation, inhibition of apoptosis, secretion of growth factors, angiogenesis, and decreased sensitivity to treatment. As a result, she said, tyrosine kinase is believed to be an important target for breast cancer therapy.
Gefitinib is a potent small molecule inhibitor of EGFR tyrosine kinase. Preclinical research has shown that gefitinib inhibits the growth of breast cancer cell lines in human breast xenograft models, and a few patients with end-stage breast cancer have achieved stable disease in early phase I trials.
Eligible patients in the current multi-center phase II, open-label trial had measurable metastatic breast cancer that was actively progressing. They were fully ambulatory, with an adequate laboratory profile. No upper or lower limit was placed on prior chemotherapy or hormonal therapy, and paraffin(Drug information on paraffin)-embedded tumor had to be available.
Patients began treatment with 500 mg/d of gefitinib. Treatment was continued until disease progression or prohibitive toxicity, and response was evaluated every 2 months. Dose interruptions of up to 14 days were allowed for adverse events, with dose reductions to 250 mg if needed.
The study enrolled 63 patients, with a median age of 52 years (range, 34 to 81); 43% had estrogen-receptor-positive tumors; 27% had HER-2 3+ tumors by immunohistochemistry; and 79% had visceral disease.
