title: Neurotoxicity as a prognostic factor in patients with metastatic breast cancer treated with ixabepilone as a first-line therapy.
abstract: OBJECTIVE
  This study is a longitudinal follow-up of metastatic breast cancer patients treated with ixabepilone as first-line chemotherapy, with the aim to evaluate the association between a mechanism-based neurotoxicity and the efficacy of ixabepilone.
  
  
  METHODS
  At the 2 main investigational sites of a phase II clinical trial, 50 patients previously treated with anthracycline received ixabepilone. A chart review was performed to evaluate overall survival (OS) and time to progression (TTP) and to describe the subsequent treatments.
  
  
  RESULTS
  The severe neurotoxicity induced by ixabepilone (38%) is correlated with a higher overall response rate to ixabepilone (79 vs. 48%; p = 0.042), a longer TTP (11.4 vs. 6.8 months; p = 0.023) and a longer OS (36.6 vs. 19.9 months; p = 0.05). After ixabepilone discontinuation, patients received a median of 4 subsequent chemotherapy lines (range 1-12). Among the 31 patients who received taxanes, neither the neurotoxicity incidence under treatment with taxanes nor the response was affected by a previous occurrence under ixabepilone treatment.
  
  
  CONCLUSIONS
  These findings suggest that neurotoxicity development under ixabepilone treatment is a predictor of treatment outcomes as well as a favorable prognostic factor. It highlights the risk-to-benefit ratio issue of ixabepilone. We noticed the possibility to treat patients with taxanes after ixabepilone without systematic recurrent neurotoxicity.
authors.affiliation: Centre Jean Perrin, Université d'Auvergne, Clermont-Ferrand, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Durando
authors.forename: Florence
authors.initials: F
authors.lastname: Dalenc
authors.forename: Catherine
authors.initials: C
authors.lastname: Abrial
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Mouret-Reynier
authors.forename: Pauline
authors.initials: P
authors.lastname: Herviou
authors.forename: Fabrice
authors.initials: F
authors.lastname: Kwiatkowski
authors.forename: Philippe
authors.initials: P
authors.lastname: Chollet
authors.forename: Henri
authors.initials: H
authors.lastname: Roche
authors.forename: Emilie
authors.initials: E
authors.lastname: Thivat
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017322:Clinical Trials, Phase II as Topic; D034261:Epothilones / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000188:drug therapy*; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D034261:Epothilones; D043823:Taxoids; C430592:ixabepilone