title: Phase II trial of fulvestrant with metronomic capecitabine for postmenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer.
abstract: BACKGROUND
  In this phase II study, we explored efficacy and toxicity of combined endocrine and low-dose metronomic chemotherapy therapy consisting of fulvestrant and capecitabine in estrogen and/or progesterone receptor-positive, HER2-negative MBC.
  
  
  METHODS
  Patients with ≤ 1 previous hormonal treatment in the metastatic setting received an injection fulvestrant loading dose 500 mg on day 1, 250 mg on days 15 and 29 followed by 250 mg every 28 days along with continuous oral capecitabine in divided doses. The total fixed daily dose of capecitabine was either 1500 mg or 2000 mg, depending on the patient's weight (< 80 kg vs. ≥ 80 kg). Primary end points were PFS and TTP. Toxicity was assessed by continuous evaluations of treatment-emergent adverse events (AEs) and changes from baseline in laboratory values.
  
  
  RESULTS
  Forty-one women, with a mean age of 64.5 years, were enrolled. Patients completed a median of 11 monthly treatment cycles. Median PFS was 14.98 months (95% confidence interval [CI], 7.26-upper limit [UL] not estimated) and median TTP was 26.94 months (95% CI, 7.26-UL not estimated). Median overall survival was 28.65 months (95% CI, 23.95-UL not estimated). Treatment was well tolerated with < 10% Grade 3 palmar-plantar erythrodysesthesia. Overall, the most frequent AEs were palmar-plantar erythrodysesthesia, fatigue, and nausea.
  
  
  CONCLUSIONS
  Fulvestrant with metronomic capecitabine demonstrates substantial activity in hormone receptor-positive MBC and is well tolerated. Combined chemoendocrine approaches should be further explored considering the low toxicity of the combination with meaningful TTP.
authors.affiliation: The West Clinic, Memphis, TN. Electronic address: lschwartzberg@westclinic.com.
authors.forename: Lee S
authors.initials: LS
authors.lastname: Schwartzberg
authors.affiliation: Advanced Medical Specialties, Miami, FL.
authors.forename: Grace
authors.initials: G
authors.lastname: Wang
authors.affiliation: The West Clinic, Memphis, TN.
authors.forename: Bradley G
authors.initials: BG
authors.lastname: Somer
authors.affiliation: Tennessee Oncology, Nashville, TN.
authors.forename: L Johnetta
authors.initials: LJ
authors.lastname: Blakely
authors.affiliation: The West Clinic, Memphis, TN.
authors.forename: Benton M
authors.initials: BM
authors.lastname: Wheeler
authors.affiliation: ACORN Research, LLC, Memphis, TN.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Walker
authors.affiliation: ACORN Research, LLC, Memphis, TN.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Stepanski
authors.affiliation: ACORN Research, LLC, Memphis, TN.
authors.forename: Arthur C
authors.initials: AC
authors.lastname: Houts
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077267:Fulvestrant; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017698:Postmenopause; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis
chemical_list: D000069287:Capecitabine; D003841:Deoxycytidine; D004958:Estradiol; D005472:Fluorouracil; D000077267:Fulvestrant; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human
keywords: Chemoendocrine; ER-/PR-positive; Faslodex; Low dose chemotherapy; Progression-free survival; Xeloda