title: Aprepitant as salvage antiemetic therapy in breast cancer patients receiving doxorubicin and cyclophosphamide.
abstract: OBJECTIVE
  To assess the efficacy of adding aprepitant to a 5-HT(3) antagonist and dexamethasone as salvage antiemetic therapy for breast cancer patients receiving their initial cycle of an anthracycline and cyclophosphamide (AC) and failing to achieve complete control of emesis.
  
  
  METHODS
  Eligibility: breast cancer patients receiving their first cycle of AC.
  
  
  METHODS
  standard dose of a 5-HT(3) antagonist and dexamethasone 8-10 mg IV/PO on day 1 prior to cycle 1 of AC and dexamethasone 4 mg bid on days 2 and 3. Patients without complete control (no emesis, no nausea, or rescue antiemetics) during cycle 1 could proceed to cycle 2. During cycle 2, patients received AC and identical antiemetics (except dexamethasone 4 mg qd on days 2 and 3) plus aprepitant 125 mg PO day 1 and 80 mg PO days 2 and 3. Primary endpoint: complete control, 0-120 h after chemotherapy.
  
  
  RESULTS
  Sixty-two patients received cycle 1 of AC. Complete control cycle 1: 13 patients (21%; 95%CI, 12-33%). Of the 49 patients eligible for cycle 2, four elected not to continue on study. Of the 45 patients receiving cycle 2, 44 were evaluable. Complete control and complete response (no emesis, no rescue) for the 5-day study period improved from 0% to 18% (p = 0.14) and 7% to 36% (p = 0.02) on cycles 1 and 2, respectively.
  
  
  CONCLUSIONS
  In breast cancer patients receiving AC, the addition of aprepitant to a 5-HT(3) antagonist and dexamethasone during cycle 2 of treatment improved antiemetic outcome. Although the improvement in the primary endpoint of complete control during cycle 2 was not significant, all secondary endpoints such as complete response and no emesis rates were significantly better during cycle 2. The extent of antiemetic control during cycle 2 was numerically inferior to the results achieved in a phase III trial employing aprepitant with cycle 1 of AC chemotherapy, suggesting that the preferred approach is to include aprepitant with the initial cycle of AC chemotherapy.
authors.affiliation: Medical Oncology, Caritas St. Elizabeth's Medical Center of Boston, HOQ Room 223, 736 Cambridge Street, Boston, MA 02135, USA. phesketh@massmed.org
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Hesketh
authors.forename: Jerry
authors.initials: J
authors.lastname: Younger
authors.forename: Pedro
authors.initials: P
authors.lastname: Sanz-Altamira
authors.forename: Melissa
authors.initials: M
authors.lastname: Hayden
authors.forename: Julie
authors.initials: J
authors.lastname: Bushey
authors.forename: Brian
authors.initials: B
authors.lastname: Trainor
authors.forename: Michael
authors.initials: M
authors.lastname: Krentzin
authors.forename: Peter
authors.initials: P
authors.lastname: Nowd
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Arnaoutakis
authors.forename: Ann M
authors.initials: AM
authors.lastname: Hesketh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000932:Antiemetics / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D000077608:Aprepitant; D001943:Breast Neoplasms / Q000188:drug therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage / Q000627:therapeutic use*; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D011446:Prospective Studies; D016879:Salvage Therapy / Q000379:methods; D013997:Time Factors; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D000932:Antiemetics; D009025:Morpholines; D000077608:Aprepitant; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide