title: Phase I/II trial of vinorelbine and sorafenib in metastatic breast cancer.
abstract: OBJECTIVE
  We investigated the efficacy and toxicity of sorafenib, a multikinase inhibitor of vascular endothelial growth factor receptor tyrosine kinase, in combination with vinorelbine therapy in a phase I/II trial in patients with metastatic breast cancer.
  
  
  METHODS
  We enrolled 11 patients in the phase I portion to determine the maximum tolerated dose (MTD) of the combination, followed by 35 extra patients treated at the MTD in phase II. The median age of patients was 54 years old (range, 31-72 years old). Tumors were estrogen receptor and progesterone receptor (ER/PR) positive in 54% (22/54) of patients, and triple negative (ER(-), PR(-), HER2(-)) in 41% (17/54) of patients. Of all patients, 22% received sorafenib and vinorelbine as first-line therapy, 37% as second-line therapy, and 41% as third-line therapy.
  
  
  RESULTS
  In total, 41 patients were treated at the MTD (6 during phase I; 35 in phase II). The observed 44% 4-month progression-free survival rate was similar to the estimated historical rate of 43% with vinorelbine treatment. The combination was tolerated with expected toxicities. Patients treated at the MTD who had received prior bevacizumab treatment received a median of 1.5 cycles (range, 1-10 cycles) compared with a median of 5 cycles (range, 2-12 cycles) for patients without prior bevacizumab treatment.
  
  
  CONCLUSIONS
  Further evaluation of vinorelbine and sorafenib in bevacizumab-naive patients may be of interest if specific biomarkers guiding patient selection can be identified.
authors.affiliation: Division of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA. Electronic address: tluu@coh.org.
authors.forename: Thehang
authors.initials: T
authors.lastname: Luu
authors.affiliation: Department of Biostatistics, City of Hope, Duarte, CA.
authors.forename: Paul
authors.initials: P
authors.lastname: Frankel
authors.affiliation: Division of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA.
authors.forename: Cathie
authors.initials: C
authors.lastname: Chung
authors.affiliation: Division of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA.
authors.forename: Warren
authors.initials: W
authors.lastname: Chow
authors.affiliation: Division of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA.
authors.forename: Joanne
authors.initials: J
authors.lastname: Mortimer
authors.affiliation: Division of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA.
authors.forename: Arti
authors.initials: A
authors.lastname: Hurria
authors.affiliation: Division of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA. Electronic address: gsomlo@coh.org.
authors.forename: George
authors.initials: G
authors.lastname: Somlo
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives; D010671:Phenylurea Compounds / Q000008:administration & dosage; D011379:Prognosis; D000077157:Sorafenib; D015996:Survival Rate; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D010671:Phenylurea Compounds; D009536:Niacinamide; D014747:Vinblastine; D000077157:Sorafenib; D000077235:Vinorelbine
keywords: Bevacizumab; Kinase inhibitor; Metastatic breast cancer; Sorafenib; Vinorelbine