title: Failure of higher-dose paclitaxel to improve outcome in patients with metastatic breast cancer: cancer and leukemia group B trial 9342.
abstract: OBJECTIVE
  Cancer and Leukemia Group B Protocol 9342 was initiated to determine the optimal dose of paclitaxel administered as a 3-hour infusion every 3 weeks to women with metastatic breast cancer.
  
  
  METHODS
  Four hundred seventy-four women with metastatic breast cancer who had received one or no prior chemotherapy regimens were randomly assigned to one of three paclitaxel dosing regimens-175 mg/m(2), 210 mg/m(2), or 250 mg/m(2)-each administered as a 3-hour infusion every 3 weeks. Women completed self-administered quality of life and symptom assessment questionnaires at baseline and after three cycles of treatment.
  
  
  RESULTS
  No evidence of a significant dose-response relationship was demonstrated over the dose range assessed. Response rates were 23%, 26%, and 21% for the three regimens, respectively. A marginally significant association (P =.04) was seen between dose and time to progression; however, in a multivariate analysis, the difference was even less apparent. No statistically significant difference was seen in survival. Neurotoxicity and hematologic toxicity were more severe on the higher dose arms. There was no significant difference in quality of life on the three arms.
  
  
  CONCLUSIONS
  Higher doses of paclitaxel administered as a 3-hour infusion to women with metastatic breast cancer did not improve response rate, survival, or quality of life. There was a slight improvement in time to progression with higher dose therapy, which was offset by greater toxicity. When a 3-hour infusion of paclitaxel is administered every 3 weeks, 175 mg/m(2) should be considered the optimal dose.
authors.affiliation: Dana-Farber Cancer Institute, 44 Binney St, D1210, Boston, MA 02115, USA. ewiner@partners.org
authors.forename: Eric P
authors.initials: EP
authors.lastname: Winer
authors.forename: Donald A
authors.initials: DA
authors.lastname: Berry
authors.forename: Susan
authors.initials: S
authors.lastname: Woolf
authors.forename: David
authors.initials: D
authors.lastname: Duggan
authors.forename: Alice
authors.initials: A
authors.lastname: Kornblith
authors.forename: Lyndsay N
authors.initials: LN
authors.lastname: Harris
authors.forename: Richard A
authors.initials: RA
authors.lastname: Michaelson
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Kirshner
authors.forename: Gini F
authors.initials: GF
authors.lastname: Fleming
authors.forename: Michael C
authors.initials: MC
authors.lastname: Perry
authors.forename: Mark L
authors.initials: ML
authors.lastname: Graham
authors.forename: Stewart A
authors.initials: SA
authors.lastname: Sharp
authors.forename: Roger
authors.initials: R
authors.lastname: Keresztes
authors.forename: I Craig
authors.initials: IC
authors.lastname: Henderson
authors.forename: Clifford
authors.initials: C
authors.lastname: Hudis
authors.forename: Hyman
authors.initials: H
authors.lastname: Muss
authors.forename: Larry
authors.initials: L
authors.lastname: Norton
mesh_terms: D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D016015:Logistic Models; D015999:Multivariate Analysis; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology; D011788:Quality of Life; D015996:Survival Rate; D017211:Treatment Failure; D014481:United States / Q000453:epidemiology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel