title: A Phase II trial of split, low-dose docetaxel and low-dose capecitabine: a tolerable and efficacious regimen in the first-line treatment of patients with HER2/neu-negative metastatic breast cancer.
abstract: BACKGROUND
  Successful therapeutic regimens in metastatic breast cancer (MBC) must balance efficacy and tolerability. Docetaxel/capecitabine is an active and commonly used doublet in this setting. Docetaxel upregulates thymidine phosphorylase and thus potentiates the antitumor effects of capecitabine. A schedule with split, low-dose docetaxel in combination with low-dose capecitabine could improve the therapeutic index of this regimen without compromising its clinical activity.
  
  
  METHODS
  Patients with previously untreated HER2/neu-negative MBC were eligible. Treatment consisted of docetaxel 25 mg/m2 on days 1 and 8 in combination with capecitabine 750 mg/m2 twice daily on days 1-14 of a 3-week cycle. Thirty-nine women were enrolled. Median age was 55 years (range, 36-75 years). Fourteen patients had triple-negative disease. Sites of metastasis were as follows: bone (n = 27); liver (n = 15); lung (n = 17); nonregional chest (n = 4); lymph nodes (n = 2); and skin (n = 1). Six patients had bone-only disease. All subjects had a performance status of 0/1. A total of 329 cycles were administered (median, 6; range, 1-50).
  
  
  RESULTS
  Of 37 patients who received study treatment, 32 had evaluable disease, 1 had a complete response, and 15 had a partial response (overall response rate was 50% in evaluable patients and 43% in the intent-to-treat analysis). Six patients had stable disease. The overall clinical benefit rate was 69% for patients with evaluable disease and 60% overall. Fifteen patients had disease that progressed or had been withdrawn from study at the time of first evaluation. With a median follow-up of 25 months, median time to treatment failure was 4.25 months (95% CI, 1.5-7 months), and median overall survival has not yet been reached. Toxicity was moderate: 15 patients (41%) had grade 3/4 adverse events.
  
  
  CONCLUSIONS
  Split, low-dose docetaxel and low-dose capecitabine is an active combination in the first-line treatment of patients with MBC. Toxicity with this schedule was manageable, making it an attractive regimen for further study in combination with targeted agents.
authors.affiliation: Division of Hematology and Oncology, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Orlando
authors.initials: O
authors.lastname: Silva
authors.forename: Gilberto
authors.initials: G
authors.lastname: Lopes
authors.forename: Daniel
authors.initials: D
authors.lastname: Morgenzstern
authors.forename: Christopher
authors.initials: C
authors.lastname: Lobo
authors.forename: Philomena
authors.initials: P
authors.lastname: Doliny
authors.forename: Edgardo
authors.initials: E
authors.lastname: Santos
authors.forename: Sakher
authors.initials: S
authors.lastname: Abdullah
authors.forename: Umang
authors.initials: U
authors.lastname: Gautam
authors.forename: Isildinha
authors.initials: I
authors.lastname: Reis
authors.forename: Catherine
authors.initials: C
authors.lastname: Welsh
authors.forename: Joyce
authors.initials: J
authors.lastname: Slingerland
authors.forename: Judith
authors.initials: J
authors.lastname: Hurley
authors.forename: Stefan
authors.initials: S
authors.lastname: Gluck
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D000077143:Docetaxel; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000069287:Capecitabine; D003841:Deoxycytidine; D000077143:Docetaxel; D005472:Fluorouracil; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids