title: Efficacy and safety of trastuzumab as a single agent in heavily pretreated patients with HER-2/neu-overexpressing metastatic breast cancer.
abstract: OBJECTIVE
  The human epidermal growth factor receptor 2 (HER2) protein is a unique and useful target for antibody therapy against breast cancers that overexpress the HER-2/neu gene. The recombinant humanized anti-HER2 monoclonal antibody, trastuzumab, was approved for clinical use in the United States in 1998. It became available in Japan in June 2001. This study focuses on the efficacy and safety of trastuzumab as a single agent in second-third line treatment of HER2/neu-overexpressing metastatic breast cancer.
  
  
  METHODS
  Between June 2001 and May 2002, we treated 62 patients with trastuzumab, as a single agent or in combination chemotherapy, for second-third line treatment of HER2-overexpressing metastatic breast cancer. Twenty-seven of 62 patients were treated with trastuzumab as a single agent. We reviewed retrospectively the efficacy and safety of the drug given as a single agent. The expression of HER2 was determined by immunohistochemical staining. All patients received a standard loading dose of 4 mg/kg followed by 2 mg/kg weekly.
  
  
  RESULTS
  Patients received a median of 16.7 weekly infusions (range, 1-66 infusions). Trastuzumab therapy was generally well tolerated. Clinically severe adverse events (grade 3 or 4) included hypotension (7.4%), and hypoxia (3.7%). Grade 1 to 2 toxicity included fever (11.1%) and diarrhea (3.7%). Infusion-related reactions were infrequent, as were serious hematologic complications. Cardiotoxicity did not occur in the study. Three patients had a complete and 3 a partial response, 3 had no change, 17 had progressive disease, and one was not evaluated. The overall response rate in the 26 patients with available data was 23.1% (95% confidence interval, 5.7-40.4). The median duration of response was 6.4 months (range, 2.5-14.0). The median time to progression was 3.1 months (range, 0.2-16.7). Response rates differed by metastatic site as follows: lung 0% (0/12), bone 10.0% (1/10), liver 0% (0/8), skin 50.0% (4/8), lymph nodes 42.9% (3/7), brain 0% (0/2).
  
  
  CONCLUSIONS
  Molecular target therapy with trastuzumab appears safe and is generally well tolerated. For treatment of metastatic breast cancer, single agent therapy produces a durable response in some patients but lacks sufficient efficacy. Single agent use of trastuzumab is a viable option for treatment in cases with non-life-threatening disease without visceral metastasis.
authors.affiliation: Department of Medical Oncology, Cancer Institute Hospital and Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo, Japan. sawapi@qc4.so-net.ne.jp
authors.forename: Masataka
authors.initials: M
authors.lastname: Sawaki
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ito
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Tada
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Mizunuma
authors.forename: Shunji
authors.initials: S
authors.lastname: Takahashi
authors.forename: Noboru
authors.initials: N
authors.lastname: Horikoshi
authors.forename: Fujio
authors.initials: F
authors.lastname: Kasumi
authors.forename: Futoshi
authors.initials: F
authors.lastname: Akiyama
authors.forename: Goi
authors.initials: G
authors.lastname: Sakamoto
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Imai
authors.forename: Akimasa
authors.initials: A
authors.lastname: Nakao
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Hatake
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D012189:Retrospective Studies; D000068878:Trastuzumab; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab