title: Phase I study of capecitabine in combination with temozolomide in the treatment of patients with brain metastases from breast carcinoma.
abstract: BACKGROUND
  A single-institution Phase I clinical trial was conducted to determine the maximum tolerated dose (MTD) and define the safety profile of temozolomide and capecitabine when used in combination to treat brain metastases from breast cancer.
  
  
  METHODS
  Patients were eligible if they had bidimensionally measurable supratentorial or infratentorial brain metastasis from histologically confirmed breast carcinoma. Patients could have received up to 3 prior chemotherapy regimens. Temozolomide and capecitabine were administered concomitantly to 4 sequential cohorts at different dosing levels on Days 1-5 and Days 8-12, with cycles repeated every 21 days until disease progression.
  
  
  RESULTS
  Twenty-four patients with multiple brain lesions were treated, including 14 patients with newly diagnosed brain metastases and 10 patients with recurrent brain metastases. Only 1 patient was chemotherapy-naive. Fatigue and nausea were the most commonly observed toxicities observed at any dose levels. Significant antitumor activity was observed, with a total of 1 complete and 3 partial responses (18% objective response rate) in the brain. The median response duration was 8 weeks (range, 6-64 weeks) and the median time to progression in the brain was 12 weeks (range, 3-70 weeks). Neurocognitive function improved or remained stable in patients with a response or stable disease.
  
  
  CONCLUSIONS
  The combination of temozolomide and capecitabine is an active, well-tolerated regimen. The observed antitumor activity warrants further evaluation of this combination as an alternative to or in combination with whole-brain radiation therapy for the treatment of multiple brain metastases.
authors.affiliation: Department of Breast Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA. rivera@edgardoriveramd.com
authors.forename: Edgardo
authors.initials: E
authors.lastname: Rivera
authors.forename: Christina
authors.initials: C
authors.lastname: Meyers
authors.forename: Morris
authors.initials: M
authors.lastname: Groves
authors.forename: Vicente
authors.initials: V
authors.lastname: Valero
authors.forename: Deborah
authors.initials: D
authors.lastname: Francis
authors.forename: Banu
authors.initials: B
authors.lastname: Arun
authors.forename: Kristine
authors.initials: K
authors.lastname: Broglio
authors.forename: Guosheng
authors.initials: G
authors.lastname: Yin
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: Thomas
authors.initials: T
authors.lastname: Buchholz
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000069287:Capecitabine; D015331:Cohort Studies; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives; D006801:Humans; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D000077204:Temozolomide; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
chemical_list: D003841:Deoxycytidine; D000069287:Capecitabine; D003606:Dacarbazine; D005472:Fluorouracil; D000077204:Temozolomide