title: Phase II study of gemcitabine and carboplatin in metastatic breast cancers with prior exposure to anthracyclines and taxanes.
abstract: BACKGROUND
  Patients with metastatic breast cancer (MBC) are usually exposed to both anthracyclines and taxanes during neoadjuvant or adjuvant treatment of primary breast cancer or during initial therapy of MBC. We investigate the combination of gemcitabine and carboplatin in MBC with prior exposure to both anthracyclines and taxanes.
  
  
  METHODS
  MBC patients previously treated with anthracyclines and taxanes were enrolled in a single tertiary center phase II study. Treatment consisted of gemcitabine (1,000 mg/m(2) I.V on days 1 and 8) and carboplatin (AUC 5 I.V on day 1) administered every 3 weeks. Results 41 patients were recruited. Objective response rate was 39% including 1 complete response (2%) and 15 partial responses (37%). Twelve patients (29%) had stable disease. Median time to progression was 4.6 months (95% CI 3.3-5.9 months) and median overall survival 10.5 months (95% CI 7.6-13.4 months). Grade 3 & 4 hematological toxicities included neutropenia (58%), febrile neutropenia (15%), anemia (12%) and thrombocytopenia (49%), including 7% who required platelet transfusions. Non-hematological toxicity was rarely severe. 56% of patients required at least one dose reduction; the mean relative dose intensity for gemcitabine and carboplatin were 0.82 (range 0.5-1.0) and 0.95 (range 0.75-1.00) respectively, with no difference in dose intensity between responders and non-responders.
  
  
  CONCLUSIONS
  Gemcitabine combined with carboplatin has promising efficacy in MBC with prior treatment with anthracyclines and taxanes but has significant haematological toxicities requiring dose modifications. The regimen may be modified to gemcitabine 800 mg/m(2) days 1 and 8 to improve tolerability.
authors.affiliation: Department of Haematology-Oncology, National University Hospital, Singapore, 5, Lower Kent Ridge Road, Singapore, 119074, Singapore.
authors.forename: Daniel
authors.initials: D
authors.lastname: Chan
authors.forename: Wee-Lee
authors.initials: WL
authors.lastname: Yeo
authors.forename: Maricel
authors.initials: M
authors.lastname: Tiemsim Cordero
authors.forename: Chiung-Ing
authors.initials: CI
authors.lastname: Wong
authors.forename: Benjamin
authors.initials: B
authors.lastname: Chuah
authors.forename: Ross
authors.initials: R
authors.lastname: Soo
authors.forename: Sing-Huang
authors.initials: SH
authors.lastname: Tan
authors.forename: Siew-Eng
authors.initials: SE
authors.lastname: Lim
authors.forename: Boon-Cher
authors.initials: BC
authors.lastname: Goh
authors.forename: Soo-Chin
authors.initials: SC
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D016190:Carboplatin / Q000009:adverse effects / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D043823:Taxoids / Q000627:therapeutic use*; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D043823:Taxoids; D003841:Deoxycytidine; D016190:Carboplatin; D000093542:Gemcitabine
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