title: Bevacizumab in Combination with Modified FOLFOX6 in Heavily Pretreated Patients with HER2/Neu-Negative Metastatic Breast Cancer: A Phase II Clinical Trial.
abstract: BACKGROUND
  Bevacizumab combined with modified FOLFOX6 is a standard regimen for colorectal cancer. The present study was to determine the efficacy and safety of bevacizumab-modified FOLFOX6 regimen in heavily pretreated patients with human epidermal growth factor receptor 2 (HER2/neu)-negative MBC.
  
  
  METHODS
  Bevacizumab, 5 mg/kg every two weeks or 7.5 mg/kg every three weeks, was administered with modified FOLFOX6 (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-FU 400 mg/m2 on day 1, followed by 5-FU 2400 mg/m2 intravenous infusion over 46 hours every 2 weeks) to patients who failed at least 1 chemotherapy regimen in the metastatic setting. The primary objective was progression free survival (PFS). Secondary objectives included objective response rate (ORR), clinical benefit rate (CBR), overall survival (OS), safety, and the change of tumor size and Eastern Cooperative Oncology Group (ECOG) performance status.
  
  
  RESULTS
  69 patients were enrolled. The median PFS was 6.8 months (95% CI, 5.0 to 8.5 months), ORR was 50.0% and median OS was 10.5 months (95% CI, 7.9 to 13.1 months). Patients showing objective responses had a 4.2-month median PFS gain and 5.7-month median OS gain compared with those who did not (P < 0.05). Grade 3 or 4 adverse events occurring in more than one patient were neutropenia (53/69, 76.8%), leukopenia (36/69, 52.2%), thrombocytopenia (13/69, 18.8%), anemia (3/69, 4.3%) and hypertension (3/69, 4.3%).
  
  
  CONCLUSIONS
  Adding bevacizumab to modified FOLFOX6 does have significant anti-tumor activity and good safety profile in heavily pretreated HER2/neu-negative MBC patients. Further trials are required to confirm whether the high ORR can translate into a long-term PFS and even OS benefit.
  
  
  BACKGROUND
  www.clinicaltrials.gov NCT01658033.
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Biyun
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Faculty of Medicine, School of Population & Public Health, University of British Columbia, Vancouver, B.C., V6T 1Z4, Canada.
authors.forename: Joseph
authors.initials: J
authors.lastname: Ragaz
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Si
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Lv
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Leiping
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Ni
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
authors.forename: Xichun
authors.initials: X
authors.lastname: Hu
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases; D019233:Retreatment; D016896:Treatment Outcome
chemical_list: D000068258:Bevacizumab; D005472:Fluorouracil; D002955:Leucovorin; D009944:Organoplatinum Compounds; D018719:Erb-b2 Receptor Tyrosine Kinases