title: Efficacy and toxicity of vinorelbine with doxorubicin/cyclophosphamide combination chemotherapy in a phase I-II study for advanced or recurrent breast cancer patients.
abstract: BACKGROUND
  To evaluate the efficacy and toxicity of vinorelbine (VNB) with doxorubicin/cyclophosphamide (AC) combination chemotherapy, a phase I-II study was carried out in patients with advanced or recurrent breast cancer.
  
  
  METHODS
  The phase I part of this study was carried out to determine the treatment schedule and acceptable dose of VNB for the phase II study. In phase I, VNB was initially given as a short infusion on days 1, 8 and 15, every 4 weeks. The initial dose of vinorelbine was 15 mg/m2. In the AC regimen, 20 mg/m2 of doxorubicin (ADM) was given intravenously (i.v.) on days 1 and 8, and 100 mg/body of cyclophosphamide (CPA) was administered orally from days 1 to 14. Subsequently, a phase II study was carried out at the maximum acceptable dose (MAD).
  
  
  RESULTS
  Twenty-three patients were entered into this study. In patients receiving VNB at a dose of 15 mg/m2, neutropenia (> or = grade 3) frequently occurred on day 15. The treatment schedule of this study was therefore changed to VNB given i.v. on days 1 and 8 with AC combination chemotherapy. In this treatment schedule, grade 4 neutropenia lasting for more than 4 days occurred in patients given VNB at a dose of 20 mg/m2 with AC more frequently than in those given 15 mg/m2 of VNB. Therefore, the MAD of VNB was determined to be 20 mg/m2 in this regimen. At this recommended dose, there were 1 complete (CR) and 8 partial responses (PRs) in 15 patients, with an overall response rate of 60.0%. No treatment-related death occurred.
  
  
  CONCLUSIONS
  These data indicate that VNB plus AC combination chemotherapy was effective and well tolerated for breast cancer patients. A randomized trial of VNB plus AC vs. AC combination chemotherapy may be required to ascertain the benefit of this regimen for advanced or recurrent breast cancer patients.
authors.affiliation: Department of Surgery, National Shikoku Cancer Center Hospital, Matsuyama.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Saeki
authors.forename: Shigemitsu
authors.initials: S
authors.lastname: Takashima
authors.forename: Masami
authors.initials: M
authors.lastname: Ogita
authors.forename: Toshio
authors.initials: T
authors.lastname: Tabei
authors.forename: Isamu
authors.initials: I
authors.lastname: Adachi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tamura
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Takatsuka
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kanda
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D002423:Cause of Death; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D009367:Neoplasm Staging; D018579:Patient Selection; D011379:Prognosis; D018570:Risk Assessment; D015996:Survival Rate; D016896:Treatment Outcome; D014747:Vinblastine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077235:Vinorelbine
chemical_list: D014747:Vinblastine; D004317:Doxorubicin; D003520:Cyclophosphamide; D000077235:Vinorelbine