title: Tolerability of and adherence to combination oral therapy with gefitinib and capecitabine in metastatic breast cancer.
abstract: OBJECTIVE
  This phase I study explored gefitinib (G) and capecitabine (C) in metastatic breast cancer (MBC).
  
  
  METHODS
  Sequential cohorts (n = 3) received G and escalating C on a 14 day on/7 day off schedule, with a validation cohort (n = 10) at the maximum tolerated dose (MTD). Dose limiting toxicity (DLT) was defined in cycle 1. The primary endpoint was safety; secondary endpoints included response and adherence.
  
  
  RESULTS
  About 19 patients were treated for a median of 5 cycles. No patients in sequential cohorts experienced DLT; C MTD was 2,000 mg/m(2)/day when paired with daily G 250 mg. In the validation cohort, four experienced serious toxicities, including diarrhea, mucositis, and palmarplantar dysesthesia. At the MTD, 6 (46%) required a C dose reduction, and 3 (23%) came off study for toxicity. One partial response was observed (8%, 95% CI 0.2-38.5%); five had stable disease >24 weeks (26, 95% CI 9-51%). Patients missed few drug doses, with the suggestion of overadherence to therapy.
  
  
  CONCLUSIONS
  In this phase I study of G and C in MBC, a C MTD was identified, and significant toxicity was observed. About 8% demonstrated a response, with 26% maintaining stable disease. The possibility of overadherence, as suggested in this study, may have implications for other trials of oral antineoplastic therapy.
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Mayer 224, Boston, MA 02115, USA. emayer@partners.org
authors.forename: E L
authors.initials: EL
authors.lastname: Mayer
authors.forename: A H
authors.initials: AH
authors.lastname: Partridge
authors.forename: L N
authors.initials: LN
authors.lastname: Harris
authors.forename: R S
authors.initials: RS
authors.lastname: Gelman
authors.forename: S T
authors.initials: ST
authors.lastname: Schumer
authors.forename: H J
authors.initials: HJ
authors.lastname: Burstein
authors.forename: E P
authors.initials: EP
authors.lastname: Winer
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000097:blood; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000077156:Gefitinib; D006801:Humans; D020714:Maximum Tolerated Dose; D055118:Medication Adherence; D008875:Middle Aged; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D011799:Quinazolines; D003841:Deoxycytidine; D000069287:Capecitabine; D066246:ErbB Receptors; D000077156:Gefitinib; D005472:Fluorouracil