title: Phase II trial of simple oral therapy with capecitabine and cyclophosphamide in patients with metastatic breast cancer: SWOG S0430.
abstract: BACKGROUND
  Interest in oral agents for the treatment of metastatic breast cancer (MBC) has increased because many patients prefer oral to i.v. regimens. We evaluated a simple oral combination of capecitabine with cyclophosphamide (CPA) for MBC.
  
  
  METHODS
  The trial was designed to determine whether or not combination therapy would achieve a 42% response rate (RR) using the Response Evaluation Criteria in Solid Tumors (RECIST) in MBC. Patients with two or fewer prior chemotherapy regimens for MBC were eligible. Those with estrogen receptor-positive MBC had to have progressed on endocrine therapy. Patients had measurable disease or elevated mucin (MUC)-1 antigen and received CPA, 100 mg daily on days 1-14, and capecitabine, 1,500 mg twice daily on days 8-21, in 21-day cycles.
  
  
  RESULTS
  In 96 eligible patients, the median progression-free survival (PFS) interval was 5.9 months (95% confidence interval [CI], 3.7-8.0 months) and median overall survival (OS) time was 18.8 months (95% CI, 13.1-22.0 months). The RR was 36% (95% CI, 26%-48%) in 80 patients with measurable disease. The MUC-1 antigen RR was 33% (95% CI, 20%-48%), occurring in 15 of 46 patients with elevated MUC-1 antigen. Toxicity was mild, with no treatment-related deaths.
  
  
  CONCLUSIONS
  PFS, OS, and RR outcomes with capecitabine plus CPA compare favorably with those of capecitabine monotherapy and combination therapy with bevacizumab, sorafenib, or ixabepilone. The addition of these other agents to capecitabine does not improve OS time in MBC patients, and this single-arm study does not suggest that the addition of CPA to capecitabine has this potential in an unselected MBC population. When OS prolongation is the goal, clinicians should choose single-agent capecitabine.
authors.affiliation: University of Michigan, Division of Hematology/Oncology, 24 Frank Lloyd Wright Drive, Suite A3400, PO Box 483, Ann Arbor, Michigan 48106, USA. aschott@med.umich.edu
authors.forename: Anne F
authors.initials: AF
authors.lastname: Schott
authors.forename: William E
authors.initials: WE
authors.lastname: Barlow
authors.forename: Kathy S
authors.initials: KS
authors.lastname: Albain
authors.forename: Helen K
authors.initials: HK
authors.lastname: Chew
authors.forename: James L
authors.initials: JL
authors.lastname: Wade
authors.forename: Keith S
authors.initials: KS
authors.lastname: Lanier
authors.forename: Danika L
authors.initials: DL
authors.lastname: Lew
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hayes
authors.forename: Julie R
authors.initials: JR
authors.lastname: Gralow
authors.forename: Robert B
authors.initials: RB
authors.lastname: Livingston
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
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 / Q000188:drug therapy* / Q000401:mortality; D000069287:Capecitabine; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D008875:Middle Aged; D018396:Mucin-1 / Q000032:analysis; D011446:Prospective Studies
chemical_list: C060192:MUC1 protein, human; D018396:Mucin-1; D003841:Deoxycytidine; D000069287:Capecitabine; D003520:Cyclophosphamide; D005472:Fluorouracil