title: A phase I study of an all-oral combination of vinorelbine/capecitabine in patients with metastatic breast cancer previously treated with anthracyclines and/or taxanes.
abstract: BACKGROUND
  Few overlapping toxicities and oral formulations make capecitabine plus oral vinorelbine an attractive new combination for treating patients with breast cancer. An all-oral regimen minimizes inconvenience for the patient and saves medical resources.
  
  
  METHODS
  To determine the recommended dose for this all-oral combination, we conducted a phase I study in 21 patients with metastatic breast cancer after failure of previous chemotherapy with anthracylines and/or taxanes for advanced disease. Capecitabine 1000 mg/m2 twice daily was given on days 2-7 and 9-14. Vinorelbine was administered at escalating doses of 40-80 mg/m2 on days 1 and 8 every 3 weeks. Dose escalation of vinorelbine was performed in cohorts of 3 patients, but the dose of vinorelbine could also be increased to the next level in the same patient after 3 cycles if there were no dose-limiting toxicities. In total, 173 cycles were administered (median, 8 cycles; range 1-21+ cycles).
  
  
  RESULTS
  Treatment was well tolerated: there were no grade 4 toxicities, and the only grade 3 toxicities in > 1 cycle were hand-foot syndrome and neutropenia (2% of cycles each). The maximum tolerated dose could not be determined using predefined criteria. However, in this heavily pretreated patient population, intrapatient vinorelbine dose escalation > 60 mg/m2 was rarely achieved. Thus, we considered vinorelbine 60 mg/m2 to offer the best dose level-toxicity ratio. At this dose, grade 3 toxicities occurred in only 7% of the 58 cycles administered. Among 19 evaluable patients, 7 exhibited response or stable disease lasting > 6 months, giving a clinical benefit rate of 37%. Duration of response in the 2 responding patients was 5 months and > 16 months.
  
  
  CONCLUSIONS
  The all-oral combination of capecitabine/vinorelbine is well tolerated and active in heavily pretreated patients. Oral vinorelbine 60 mg/m2 is recommended in combination with capecitabine 1000 mg/m2 twice daily for further evaluation.
authors.affiliation: Department of Oncology, Tampere University Hospital, Finland. klpike@uta.fi
authors.forename: Pirkko-Liisa
authors.initials: PL
authors.lastname: Kellokumpu-Lehtinen
authors.forename: Kaisa
authors.initials: K
authors.lastname: Sunela
authors.forename: Ilari
authors.initials: I
authors.lastname: Lehtinen
authors.forename: Heikki
authors.initials: H
authors.lastname: Joensuu
authors.forename: Johanna
authors.initials: J
authors.lastname: Sjöström-Mattson
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D001952:Bridged-Ring Compounds / Q000627:therapeutic use; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D008875:Middle Aged; D011355:Prodrugs / Q000008:administration & dosage / Q000009:adverse effects; D043823:Taxoids / Q000627:therapeutic use; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: D018943:Anthracyclines; D001952:Bridged-Ring Compounds; D011355:Prodrugs; D043823:Taxoids; D003841:Deoxycytidine; C080625:taxane; D014747:Vinblastine; D000069287:Capecitabine; D000077235:Vinorelbine; D005472:Fluorouracil