title: Phase II study of weekly intravenous trastuzumab (Herceptin) in patients with HER2/neu-overexpressing metastatic breast cancer.
abstract: The HER2/neu proto-oncogene is overexpressed in 25% to 30% of patients with breast cancer. Trastuzumab (Herceptin; Genentech, San Francisco, CA), a recombinant humanized monoclonal antibody with high affinity for the HER2 protein, inhibits the growth of breast cancer cells overexpressing HER2. In this phase II study the efficacy and toxicity of weekly administration of trastuzumab was evaluated in 46 patients with metastatic breast cancer whose tumors overexpressed HER2. A loading dose of 250 mg trastuzumab was administered intravenously, which was followed by 10 weekly doses of 100 mg each. Upon completion of this treatment period, patients with no disease progression could receive a weekly maintenance dose of 100 mg. Patients in this trial had extensive metastatic disease, and most had received prior anticancer therapy. Ninety percent of patients achieved adequate serum levels of trastuzumab. Toxicity was minimal, and no antibodies against trastuzumab could be detected. Objective responses were observed in 5 of the 43 evaluable patients, which included 1 complete remission and 4 partial remissions, for an overall response rate of 11.6%. Responses were seen in mediastinum, lymph nodes, liver, and chest wall lesions. Minor responses (seen in 2 patients) and stable disease (14 patients) lasted for a median of 5.1 months. These results demonstrate that trastuzumab is well tolerated and clinically active in patients with HER2-overexpressing metastatic breast cancers who have received extensive prior therapy. The regression of human cancer through the targeting of putative growth factor receptors such as HER2 warrants further evaluation of trastuzumab in the treatment of breast cancer.
authors.affiliation: Department of Medicine, Services of Breast and Gynecological Cancer Medicine and Clinical Immunology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: J
authors.initials: J
authors.lastname: Baselga
authors.forename: D
authors.initials: D
authors.lastname: Tripathy
authors.forename: J
authors.initials: J
authors.lastname: Mendelsohn
authors.forename: S
authors.initials: S
authors.lastname: Baughman
authors.forename: C C
authors.initials: CC
authors.lastname: Benz
authors.forename: L
authors.initials: L
authors.lastname: Dantis
authors.forename: N T
authors.initials: NT
authors.lastname: Sklarin
authors.forename: A D
authors.initials: AD
authors.lastname: Seidman
authors.forename: C A
authors.initials: CA
authors.lastname: Hudis
authors.forename: J
authors.initials: J
authors.lastname: Moore
authors.forename: P P
authors.initials: PP
authors.lastname: Rosen
authors.forename: T
authors.initials: T
authors.lastname: Twaddell
authors.forename: I C
authors.initials: IC
authors.lastname: Henderson
authors.forename: L
authors.initials: L
authors.lastname: Norton
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C000715470:MAS1 protein, human