SAN ANTONIOIn the first phase II trial of 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
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
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-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.