title: Neuropathy is not associated with clinical outcomes in patients receiving adjuvant taxane-containing therapy for operable breast cancer.
abstract: OBJECTIVE
  Neuropathy is a common and potentially disabling complication of adjuvant taxane therapy. Recent studies have identified candidate single nucleotide polymorphisms associated with taxane-induced neuropathy. Therefore, we sought to determine whether neuropathy was associated with breast cancer recurrence in a clinical trial population who received adjuvant taxane therapy.
  
  
  METHODS
  Trial E1199 included 4,554 eligible women with operable breast cancer who received up to four cycles of doxorubicin and cyclophosphamide every 3 weeks followed by paclitaxel 175 mg/m(2) every 3 weeks for four cycles (P3), paclitaxel 80 mg/m(2) weekly for 12 cycles (P1), docetaxel 100 mg/m(2) every 3 weeks for four cycles (D3), or docetaxel 35 mg/m(2) weekly for 12 cycles (D1). A Cox proportional hazards model was used to determine the relationship between neuropathy and disease-free survival (DFS), overall survival (OS), and recurrence-free survival (RFS) by treating neuropathy status as a time dependent covariate and using a landmark analysis.
  
  
  RESULTS
  Of 4,554 patients who received at least one taxane dose, grade 2 to 4 neuropathy developed in 18%, 22%, 15%, and 13% of patients in the P3, P1, D3, and D1 arms, respectively. In a model that included age, race, obesity, menopausal status, tumor size, nodal status, treatment arm, neuropathy, and hyperglycemia, no significant relationship was found between neuropathy and DFS, OS, or RFS.
  
  
  CONCLUSIONS
  There was no association between taxane-induced neuropathy and outcome.
authors.affiliation: Eastern Cooperative Oncology Group, 535 Barnhill Dr, Indiana Cancer Pavilion, Indianapolis, IN 46202, USA. bpschnei@iupui.edu
authors.forename: Bryan P
authors.initials: BP
authors.lastname: Schneider
authors.forename: Fengmin
authors.initials: F
authors.lastname: Zhao
authors.forename: Molin
authors.initials: M
authors.lastname: Wang
authors.forename: Vered
authors.initials: V
authors.lastname: Stearns
authors.forename: Silvana
authors.initials: S
authors.lastname: Martino
authors.forename: Vicky
authors.initials: V
authors.lastname: Jones
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
authors.forename: Tom
authors.initials: T
authors.lastname: Saphner
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Wolff
authors.forename: George W
authors.initials: GW
authors.lastname: Sledge
authors.forename: William C
authors.initials: WC
authors.lastname: Wood
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Davidson
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Sparano
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery*; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008408:Mastectomy / Q000009:adverse effects / Q000401:mortality; D008875:Middle Aged; D015999:Multivariate Analysis; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000401:mortality; D017239:Paclitaxel / Q000008:administration & dosage; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: D004317:Doxorubicin; D003520:Cyclophosphamide; D017239:Paclitaxel