Phase II study of receptor-enhanced chemosensitivity using recombinant humanized anti-p185HER2/neu monoclonal antibody plus cisplatin in patients with HER2/neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment

Purpose: To determine the toxicity, pharmacokinetics, response Kite, and response duration of intravenous (IV) administration of recombinant, humanized anti-p185(HER2) monoclonal antibody (rhuMAb HER2) plus cisplatin (CDDP) in a phase II, open-label, multicenter clinical trial for patients with HER2/neu-overexpressing metastatic breast cancer. Patients and Methods: The study population consisted of extensively pretreated advanced breast cancer patients with HER2/neu overexpression and disease progression during standard chemotherapy. Patients received a loading dose of rhuMAb HER2 (250 mg IV) on day 0, followed by weekly doses of 100 mg IV for 9 weeks. Patients received CDDP (75 mg/m(2)) on days 1, 29, and 57. Results: Of 37 patients assessable for response, nine (24.3%) achieved a PR, nine (24.3%) had a minor response or stable disease, and disease progression occurred in 19 (51.3%). The median response duration was 5.3 months (range, 1.6-18). Grade III or IV toxicity was observed in 22 of 39 patients (56%). The toxicity profile reflected that expected from CDDP alone with the most common toxicities being cytopenias (n = 10), nausea/vomiting (n = 9), and asthenia (n = 5). Mean pharmacokinetic parameters of rhuMAb HER2 were unaltered by coadministration of CDDP. Conclusion: The use of rhuMAb HER2 in combination with CDDP in patients with HER2/neu-overexpressing metastatic breast cancer results in objective clinical response Kites higher than those reported previously for CDDP alone, or rhuMAb HER2, alone. In addition, the combination results in no apparent increase in toxicity. Finally, the pharmacology of rhuMAb HEW was unaffected by coadministration with CDDP. J Clin Oncol 16: 2659-2671. (C) 1998 by American Society of Clinical Oncology.