title: A phase II study of ZD0473 given as a short infusion every 3 weeks to patients with advanced or metastatic breast cancer: a National Cancer Institute of Canada Clinical Trials Group trial, IND 129.
abstract: BACKGROUND
  ZD0473 is a new generation platinum compound with activity against a wide range of human tumor cell lines and xenografts, including carboplatin- and cisplatin-resistant lines. A phase II study of ZD0473 in advanced breast cancer was initiated by the National Cancer Institute of Canada Clinical Trials Group.
  
  
  METHODS
  Women with metastatic breast cancer, measurable disease, an Eastern Cooperative Oncology Group performance status of up to two, and a maximum of one prior cytotoxic agent for recurrent disease were enrolled and treated at 120 mg/m(2) every 3 weeks. After 13 patients were enrolled, the dose was increased to 150 mg/m(2) on the basis of emergent data from studies ongoing at the time.
  
  
  RESULTS
  Thirty-three women were evaluable for toxicity and 26 patients for response. Toxicity was mainly hematological with grade 3/4 thrombocytopenia in 12 of 20 patients (60%) treated at 150 mg/m(2) and grade 3 thrombocytopenia in three of 13 patients (23%) at 120 mg/m(2). Grade 3/4 neutropenia occurred in 15 patients (75%) at 150 mg/m(2) and two patients (10%) at 120 mg/m(2). Non-hematological toxicities were generally mild or moderate. There was one partial response seen for a response rate of 3.8% (95% confidence interval 0.1% to 19.5%) and stable disease in 15 patients.
  
  
  CONCLUSIONS
  ZD0473 has minor activity as a single agent in metastatic breast cancer. Combinations with other drugs including docetaxel are ongoing and may be of interest.
authors.affiliation: British Columbia Cancer Agency-Vancouver Cancer Center, Canada. kgelmon@bccancer.bc.ca
authors.forename: K A
authors.initials: KA
authors.lastname: Gelmon
authors.forename: T A
authors.initials: TA
authors.lastname: Vandenberg
authors.forename: L
authors.initials: L
authors.lastname: Panasci
authors.forename: B
authors.initials: B
authors.lastname: Norris
authors.forename: M
authors.initials: M
authors.lastname: Crump
authors.forename: L
authors.initials: L
authors.lastname: Douglas
authors.forename: W
authors.initials: W
authors.lastname: Walsh
authors.forename: S J
authors.initials: SJ
authors.lastname: Matthews
authors.forename: L K
authors.initials: LK
authors.lastname: Seymour
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009503:Neutropenia / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; C110525:amminedichloro(2-methylpyridine)platinum(II)