title: Phase II multicenter study of larotaxel (XRP9881), a novel taxoid, in patients with metastatic breast cancer who previously received taxane-based therapy.
abstract: BACKGROUND
  Treatment options are limited for patients with refractory metastatic breast cancer (MBC). Larotaxel (XRP9881) is a novel taxoid with preclinical activity against taxane-resistant breast cancer. The current phase II trial of larotaxel was conducted in women with taxane-treated MBC.
  
  
  METHODS
  Patients were stratified by response to prior taxane therapy (resistant or nonresistant). Larotaxel 90 mg/m(2) was administered as a 1-h infusion every 3 weeks. Patients were evaluated for tumor response every two cycles. A blinded external response review committee determined the overall response rate (ORR), duration of response (DOR), and time to progression (TtP) of the disease. Median survival time (MST) and safety were also evaluated.
  
  
  RESULTS
  One hundred and thirty patients were treated. In the nonresistant group, the ORR was 42%; median DOR 5.3 months; median TtP 5.4 months; and MST 22.6 months. In the resistant group, the ORR was 19%; median DOR 5.0 months; median TtP 1.6 months; and MST 9.8 months. The most common grade 3/4 adverse events were neutropenia (82%), fatigue (15%), diarrhea (12%), febrile neutropenia (9%), neutropenic infection (8%), and sensory neuropathy (7%).
  
  
  CONCLUSIONS
  Larotaxel has good activity, manageable toxicity, and a favorable therapeutic index in women with taxane-pretreated MBC.
authors.affiliation: Department of Medical Oncology, Institut Curie, Paris, France. Electronic address: veronique.dieras@curie.net.
authors.forename: V
authors.initials: V
authors.lastname: Diéras
authors.affiliation: Carolinas Hematology-Oncology Associates, Charlotte, NC, USA.
authors.forename: S
authors.initials: S
authors.lastname: Limentani
authors.affiliation: Centre Val d'Aurelle, Montpellier.
authors.forename: G
authors.initials: G
authors.lastname: Romieu
authors.affiliation: Centre René Huguenin, Saint Cloud.
authors.forename: M
authors.initials: M
authors.lastname: Tubiana-Hulin
authors.affiliation: Centre Catherine de Sienne, Nantes, France.
authors.forename: A
authors.initials: A
authors.lastname: Lortholary
authors.affiliation: Hematology/Oncology, Dartmouth/Hitchcock Medical Center, Lebanon, NH, USA.
authors.forename: P
authors.initials: P
authors.lastname: Kaufman
authors.affiliation: Department of Medical Oncology, Institut Curie, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Girre
authors.affiliation: Sanofi-aventis, Bagneux, France.
authors.forename: M
authors.initials: M
authors.lastname: Besenval
authors.affiliation: MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: V
authors.initials: V
authors.lastname: Valero
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D001952:Bridged-Ring Compounds / Q000008:administration & dosage*; D015331:Cohort Studies; D003967:Diarrhea / Q000139:chemically induced; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000473:pathology; D009503:Neutropenia / Q000139:chemically induced; D011446:Prospective Studies; D043823:Taxoids / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D043823:Taxoids; C080625:taxane; C531079:larotaxel