title: Randomized trial of 3-hour versus 24-hour infusion of high-dose paclitaxel in patients with metastatic or locally advanced breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-26.
abstract: OBJECTIVE
  Paclitaxel is an active drug for the treatment of breast cancer; however, the appropriate duration of administration is unknown. We assessed and compared the response rate, event-free survival, survival, and toxicity of paclitaxel 250 mg/m(2) delivered every 3 weeks as a 3-hour or 24-hour infusion.
  
  
  METHODS
  A total of 563 women with stage IV or IIIB breast cancer were randomized into one of two groups: 279 received 3-hour paclitaxel and 284 received 24-hour paclitaxel. Patients were stratified by age, stage of disease, and prior therapy.
  
  
  RESULTS
  A significantly higher rate of tumor response occurred in the first four cycles of therapy in patients who received the 24-hour infusion of paclitaxel (51% v 41%, respectively; P =.025). Tumor response over all cycles was also significantly higher in the group that received 24-hour infusion (54% v 44%, respectively; P =.023). There were no significant differences in event-free survival or survival between the two arms of the study (P =.9 and.8, respectively). No treatment by stage or by age interactions were observed. During the first four cycles of therapy, at least one episode of >/= grade 3 toxicity (excluding nadir hematologic values, alopecia, and weight change) occurred in 45% of patients who received the 3-hour paclitaxel infusion and in 50% of those who received the 24-hour paclitaxel infusion. Febrile neutropenia, >/= grade 3 infection, and >/= grade 3 stomatitis were less frequent, and severe neurosensory toxicity was more frequent in those who received the 3-hour paclitaxel infusion. Ten treatment-related deaths occurred in the first four cycles. Age, stage, and prior chemotherapy did not influence the effect of treatment.
  
  
  CONCLUSIONS
  When administered as a continuous 24-hour infusion, high-dose paclitaxel results in a higher tumor response rate than when administered as a 3-hour infusion but does not significantly improve event-free survival or survival. Paclitaxel as a 24-hour infusion results in increased hematologic toxicity and decreased neurosensory toxicity.
authors.affiliation: National Surgical Adjuvant Breast and Bowel Project Operations Center and Biostatistical Center, Pittsburgh, PA 15212-5234, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Smith
authors.forename: A M
authors.initials: AM
authors.lastname: Brown
authors.forename: E P
authors.initials: EP
authors.lastname: Mamounas
authors.forename: S J
authors.initials: SJ
authors.lastname: Anderson
authors.forename: B C
authors.initials: BC
authors.lastname: Lembersky
authors.forename: J H
authors.initials: JH
authors.lastname: Atkins
authors.forename: H R
authors.initials: HR
authors.lastname: Shibata
authors.forename: L
authors.initials: L
authors.lastname: Baez
authors.forename: P A
authors.initials: PA
authors.lastname: DeFusco
authors.forename: E
authors.initials: E
authors.lastname: Davila
authors.forename: S J
authors.initials: SJ
authors.lastname: Tipping
authors.forename: J D
authors.initials: JD
authors.lastname: Bearden
authors.forename: M P
authors.initials: MP
authors.lastname: Thirlwell
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel