title: Combination therapy by trastuzumab with 5'-deoxy-5-fluorouridine and cyclophosphamide in patients with metastatic breast cancer.
abstract: BACKGROUND
  Trastuzumab (Herceptin®) was clinically introduced in Japan in 2001 to treat metastatic breast cancer patients who show an over-expression of human epidermal growth factor receptor 2 (HER2). Since that time, this anticancer drug has played an important role in the treatment of cancer. In the present retrospective study, trastuzumab was administered in combination with 5'-deoxy-5-fluorouridine (5'-DFUR) and cyclophosphamide (CPM) as the third- to sixth- line therapy in 25 patients whose HER2-positive metastatic breast cancers did not respond but showed recurrence after treatment with several chemotherapeutic regimens, namely, trastuzumab alone, and trastuzumab combined with taxane or other anticancer drugs.
  
  
  METHODS
  Trastuzumab was administered at a dose of 2 mg/kg (at a loading dose of 4 mg/kg) once weekly; 5'-DFUR, at an oral daily dose of 800-1200 mg/body; and CPM, at an oral daily dose of 100 mg/body for 2 weeks followed by one week discontinuation of the drug.
  
  
  RESULTS
  The response rate to the combination therapy was 32% (95% confidence interval, 17-52%). Grade 3 adverse effects, according to National Cancer Institute-Clinical Therapeutic Conference version 2.0. (NCI-CTC ver. 2.0), included: neutropenia in 7 patients, anemia in one, and elevation of alkaline phosphatase (ALP) in one. Other adverse events of grade 1 or 2 in accordance with NCI-CTC included general fatigue, nausea, vomiting, thrombocytopenia, increased transaminase, and decreased serum albumin. All adverse events were easily controllable and reversible after discontinuation of the drug.
  
  
  CONCLUSIONS
  Combination therapy with trastuzumab, 5'-DFUR and CPM is effective and well tolerated as the third- to six line treatment option for patients with HER2-overexpressing metastatic breast cancer.
  
  
  CONCLUSIONS
  Combination therapy by trastuzumab with 5'-DFUR and cyclophosphamide can be safely administered on an outpatient basis and is useful to treat patients with HER2-overexpressing metastatic breast cancer.
authors.affiliation: Department of Surgery, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Saito
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Tokuda
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D001943:Breast Neoplasms / Q000473:pathology*; D003520:Cyclophosphamide / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D005467:Floxuridine / Q000627:therapeutic use*; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D003520:Cyclophosphamide; D005467:Floxuridine; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C025034:doxifluridine