EGF Receptor Mabs and Chemotherapy in Breast Cancer.
Annual rept. 15 Sep 96-14 Sep 97,
MEMORIAL SLOAN-KETTERING CANCER CENTER NEW YORK
Pagination or Media Count:
EGFR is a transmembrane tyrosine kinase that binds a variety of ligands including EOF, transforming growth factor-omega, and amphiregulin. Ligand binding induces activation of the tyrosine kinase leading to growth stimulation, but also perhaps to inhibition of apoptosis and other proliferative phenomena. The bioactivity of monoclonal antibodies Mabs against EGER that we have produced is well documented 1. The humanmunne chimeric version of Mab 225 HC Mab 225 has been produced by ImClone Systems. These Mabs inhibit the growth of tumors expressing EGFR and synergize with either doxorubicin or paclitaxel against well-established tumor xenografts 2-5. Preliminary clinical trials with murine anti-EGFR Mabs conducted by our group have shown that their administration is safe and that plasma levels of Mab sufficient to saturate receptors can be achieved 6,7. The present investigation is to determine the safety, feasibility, and noncomparative efficacy of chemotherapy plus Mab in the treatment of patients with metastatic breast cancer who have not received extensive prior chemotherapy for their advanced disease. After thorough review of the preclinical data Appendix A, we elected to first proceed with the study of paclitaxel and anti-EGER Mabs. This decision was also based on considerations of patient availability, since doxorubicin is now widely used in the adjuvant setting.
- Medicine and Medical Research