title: An all-oral combination of metronomic cyclophosphamide plus capecitabine in patients with anthracycline- and taxane-pretreated metastatic breast cancer: a phase II study.
abstract: OBJECTIVE
  Oral administration of cyclophosphamide (CTX) and capecitabine may have a greater potential for treatment of metastatic breast cancer (MBC) due to anti-angiogenesis resulting from the metronomic dosage and upregulation of thymidine phosphorylase by CTX. The purpose of this phase II study was to evaluate the efficacy and safety profile of an all-oral combination of metronomic CTX plus capecitabine for women with anthracycline- and taxane-pretreated MBC.
  
  
  METHODS
  In this prospective single-center, open-label, phase II trial, patients with measurable disease received oral metronomic CTX 65 mg/m(2) daily on days 1-14 plus capecitabine 1,000 mg/m(2) twice daily on days 1-14. The treatment was repeated every 3 weeks, and continued until disease progression, unacceptable toxicity or withdrawal of informed consent. The primary endpoint of the study was time to progression (TTP).
  
  
  RESULTS
  A total of 68 patients were enrolled and received 537 cycles of chemotherapy with a median of 8 cycles (range: 1-30 cycles) per patient. Sixty-six patients were evaluated for efficacy with all patients for toxicity. With a median follow-up time of 26 months, the median time to progression was 5.2 months (95% CI, 4.2-6.2 months), and the median overall survival was 16.9 months. The overall response rate was 30.3% (95% CI, 20-43%). Clinical benefit rate was 53.0% (95% CI, 38-62%). The doublet was well tolerable, with anorexia (7.5%), the only grade 3/4 adverse events occurring in more than 5% of patients. Grade 3 hand-foot syndrome was 4.4%.
  
  
  CONCLUSIONS
  The all-oral combination of metronomic CTX plus capecitabine is an effective and convenient and well-tolerated regimen for MBC. (ClinicalTrials.gov number, NCT00589901).
authors.affiliation: Department of Medical Oncology, Cancer Hospital of Fudan University, Shanghai Medical College, 270 Dongan Road, Shanghai 200032, China.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Wang
authors.forename: Jingsong
authors.initials: J
authors.lastname: Lu
authors.forename: Shiangjiin
authors.initials: S
authors.lastname: Leaw
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Hong
authors.forename: Jialei
authors.initials: J
authors.lastname: Wang
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Shao
authors.forename: Xichun
authors.initials: X
authors.lastname: Hu
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000855:Anorexia / Q000139:chemically induced; D018943:Anthracyclines / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D001952:Bridged-Ring Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000069287:Capecitabine; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D060831:Hand-Foot Syndrome / Q000209:etiology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011446:Prospective Studies; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D018943:Anthracyclines; D001952:Bridged-Ring Compounds; D043823:Taxoids; D003841:Deoxycytidine; C080625:taxane; D000069287:Capecitabine; D003520:Cyclophosphamide; D005472:Fluorouracil