title: A pilot study of adjuvant doxorubicin and cyclophosphamide followed by paclitaxel and sorafenib in women with node-positive or high-risk early-stage breast cancer.
abstract: OBJECTIVE
  To examine the safety of sorafenib combined with standard adjuvant treatment in patients with node-positive or otherwise high-risk breast cancer.
  
  
  METHODS
  Eligibility: mastectomy/breast-conserving surgery; axillary node assessment for stage I/II/IIIA/IIIC (T1-3, N3a only) breast cancer; node-positive/high-risk node-negative (tumor size >2 cm; hormone-receptor negative; grade 2/3; or age <35 years); Eastern Cooperative Oncology Group performance status (ECOG-PS) 0-1; and adequate organ function.
  
  
  METHODS
  doxorubicin (60 mg/m(2) intravenous) and cyclophosphamide (600 mg/m(2) intravenous; AC) on day 1, every 3 weeks (x 4 cycles), followed by paclitaxel 175 mg/m(2) intravenous on day 1, (every 3 weeks x 4 cycles) or 80 mg/m(2) intravenous (every week/x 12 cycles), combined with sorafenib (400 mg oral twice a week; TS) for 12 months or less.
  
  
  RESULTS
  Forty-five patients were enrolled from 5/07-1/08. Baseline characteristics included: median age of 54 years (range, 35-74 years); 93% of patients with ECOG-PS 0; 84% node-positive; 33% hormone-receptor negative. All patients completed AC treatment and were eligible to receive TS; of these, 8 (13%) patients came off study due to physician/patient decision; 21 (47%) patients came off study due to toxicity; 2 (4%) patients completed TS but did not proceed with maintenance sorafenib; and 14 (31%) patients completed TS and entered the maintenance phase of sorafenib treatment. Sorafenib was taken for 6.1 weeks during the paclitaxel phase and 15 weeks during maintenance. Severe toxicities during sorafenib therapy were limited, including neutropenia, anorexia, arthralgia, diarrhea, and dyspnea. After a median follow-up of 21.0 months (range, 18.9-25.9), all patients were alive and without recurrence.
  
  
  CONCLUSIONS
  Sorafenib was generally associated with limited severe toxicity when combined with paclitaxel following AC. However, many patients discontinued sorafenib early due to grade 1/2 toxicity, physician/patient decision, and treatment compliance. Additional studies of sorafenib in breast cancer in the neoadjuvant and triple-negative settings are warranted.
authors.affiliation: Sarah Cannon Research Institute, Nashville, TN 37203, USA. dspigel@tnonc.com
authors.forename: David R
authors.initials: DR
authors.lastname: Spigel
authors.forename: John D
authors.initials: JD
authors.lastname: Hainsworth
authors.forename: Howard A
authors.initials: HA
authors.lastname: Burris
authors.forename: David C
authors.initials: DC
authors.lastname: Molthrop
authors.forename: Nancy
authors.initials: N
authors.lastname: Peacock
authors.forename: Michael
authors.initials: M
authors.lastname: Kommor
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Vazquez
authors.forename: F Anthony
authors.initials: FA
authors.lastname: Greco
authors.forename: Denise A
authors.initials: DA
authors.lastname: Yardley
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use*; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D009536:Niacinamide / Q000031:analogs & derivatives; D017239:Paclitaxel / Q000009:adverse effects / Q000627:therapeutic use*; D010671:Phenylurea Compounds; D010865:Pilot Projects; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D000077157:Sorafenib; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D004317:Doxorubicin; D003520:Cyclophosphamide; D000077157:Sorafenib; D017239:Paclitaxel