title: A dose escalation study of leucovorin (LV) and 48-hour continuous infusion of 5-fluorouracil in combination with cyclophosphamide and vinorelbine in pretreated patients with metastatic breast cancer.
abstract: OBJECTIVE
  To determine the maximum tolerated doses (MTD) and dose-limiting toxicities (DLTs) of vinorelbine (VNR) with fixed doses of cyclophosphamide (CPM) and 5-fluorouracil/leucovorin (5-FU/LV) in patients with metastatic breast cancer (MBC) pretreated with anthracyclines and taxanes.
  
  
  METHODS
  Eighteen patients with MBC pretreated with anthracyclines and taxanes were enrolled. VNR was administered as a 10-min intravenous infusion (i.v.) on day 1 at escalated doses with CPM 300 mg/m2 i.v. bolus and LV 500 mg/m2 as a 2-hour i.v. infusion, followed by 5-FU 1500 mg/m2 as a 22-hour continuous infusion (c.i.) for two consecutive days. Treatment was repeated every two weeks.
  
  
  RESULTS
  At the dose of VNR 22.5 mg/m2 without rhG-CSF and 25 mg/m2 with rhG-CSF support, the DLT had been reached. Grade 3 or 4 neutropenia occurred in six (33%) patients and in fourteen (27%) cycles with no episode of febrile neutropenia. One (5.5%) patient developed grade 4 thrombocytopenia. Grade 3 neurotoxicity occurred in two patients and grade 2 and 3 asthenia in five (28%).
  
  
  CONCLUSIONS
  The recommended doses for phase II studies are 20 mg/m2 for VNR (22.5 mg/m2 with rhG-CSF support) and 300 mg/m2 for CPM on day 1, with 500 mg/m2 for LV and 1500 mg/m2 for 5-FU on days 1 and 2.
authors.affiliation: Department of Medical Oncology, University General Hospital of Heraklion, Heraklion, Crete, Greece. georgsec@med.uoc.gr
authors.forename: Charalambos
authors.initials: C
authors.lastname: Kouroussis
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Kalbakis
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Androulakis
authors.forename: Sophia
authors.initials: S
authors.lastname: Agelaki
authors.forename: Lambros
authors.initials: L
authors.lastname: Vamvakas
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Malas
authors.forename: John
authors.initials: J
authors.lastname: Souglakos
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Vardakis
authors.forename: Vassilis
authors.initials: V
authors.lastname: Georgoulias
mesh_terms: 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*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D043823:Taxoids / Q000627:therapeutic use; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077235:Vinorelbine
chemical_list: D018943:Anthracyclines; D043823:Taxoids; D014747:Vinblastine; D003520:Cyclophosphamide; D002955:Leucovorin; D000077235:Vinorelbine; D005472:Fluorouracil