title: A randomized phase II study of paclitaxel and bevacizumab with and without gemcitabine as first-line treatment for metastatic breast cancer.
abstract: BACKGROUND
  The addition of bevacizumab to paclitaxel improved progression-free survival (PFS) of patients with metastatic breast cancer (MBC). We examined the efficacy and safety of adding gemcitabine to paclitaxel/bevacizumab (PB).
  
  
  METHODS
  In this multicenter, open-label, randomized phase II trial, women with locally advanced or MBC were randomly assigned to receive paclitaxel 90 mg/m(2) (days 1, 8, 15) and bevacizumab 10 mg/kg (days 1, 15) with or without gemcitabine 1500 mg/m(2) (days 1, 15) in 28-day cycles. Patients with prior cytotoxic therapy for MBC were ineligible. The primary endpoint was investigator-assessed overall response rate (ORR); secondary endpoints were PFS, overall survival (OS), safety, and quality of life.
  
  
  RESULTS
  Ninety-four patients received PB, and 93 received paclitaxel/bevacizumab/gemcitabine (PB+G). The ORRs were 48.9% (95% confidence interval [CI], 38.5%-59.5%) and 58.7% (95% CI, 47.9%-68.9%; P = .117) with PB and PB+G, respectively. The median PFS was 8.8 months (95% CI, 8.1-10.4 months) and 11.3 months (95% CI, 9.7-12.7 months; P = .247; hazard ratio, 0.82); the median OS was 25.0 months (95% CI, 18.8-not assessable [N/A] months) and 24.3 months (95% CI, 20.3-N/A months; P = .475; hazard ratio, 0.84), with PB and PB+G, respectively. There was significantly more grade 3-4 neutropenia (P = .001) and dyspnea (P = .014) with PB+G. Patients treated with PB experienced more improvement in total FACT-B (Functional Assessment of Cancer Therapy-Breast) (P = .021), FACT-B Social/Family Well-being (P = .041), and Breast Cancer-Additional Concerns (P = .008) scores than patients treated with PB+G.
  
  
  CONCLUSIONS
  The addition of gemcitabine to PB was not associated with a statistically significant improvement in ORR. Treatment with PB+G increased the incidence of severe neutropenia and dyspnea, although the regimen generally was well tolerated.
authors: University of Pittsburgh School of Medicine, 300 Halket St., Pittsburgh, PA 15213, USA. brufskyam@upmc.edu
authors: Adam
authors: A
authors: Brufsky
authors: Karen
authors: K
authors: Hoelzer
authors: Thaddeus
authors: T
authors: Beck
authors: Robert
authors: R
authors: Whorf
authors: Mark
authors: M
authors: Keaton
authors: Padma
authors: P
authors: Nadella
authors: Elisa
authors: E
authors: Krill-Jackson
authors: Joan
authors: J
authors: Kroener
authors: Edward
authors: E
authors: Middleman
authors: Michael
authors: M
authors: Frontiera
authors: Devchand
authors: D
authors: Paul
authors: Timothy
authors: T
authors: Panella
authors: Jane
authors: J
authors: Bromund
authors: Luping
authors: L
authors: Zhao
authors: Mauro
authors: M
authors: Orlando
authors: Fritz
authors: F
authors: Tai
authors: Martin D
authors: MD
authors: Marciniak
authors: Coleman
authors: C
authors: Obasaju
authors: John
authors: J
authors: Hainsworth
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D011788:Quality of Life; D015996:Survival Rate; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003841:Deoxycytidine; D000068258:Bevacizumab; D017239:Paclitaxel; D000093542:Gemcitabine