title: Dose-intensive vinorelbine with concurrent granulocyte colony-stimulating factor support in paclitaxel-refractory metastatic breast cancer.
abstract: OBJECTIVE
  We evaluated weekly single-agent intravenous (IV) vinorelbine as salvage therapy for metastatic breast cancer. After the first five patients, all received elective growth factor support with granulocyte colony-stimulating factor (G-CSF; filgrastim) in an attempt to maximize delivered dose-intensity (DDI). Objective tumor response, DDI, and toxicity were assessed, as well as time to progression (TTP) and survival.
  
  
  METHODS
  This single-center nonrandomized trial enrolled 40 patients. Anthracycline exposure and subsequent progression were common to all patients, and 38 of 40 were paclitaxel-refractory. Vinorelbine was given initially at 30 mg/m2/wk, then at 35 mg/m2/wk in a phase I/II design, which involved first intermittent (6 days of 7) and then continuous (daily) administration of G-CSF at 5 micrograms/kg.
  
  
  RESULTS
  The maximum-tolerated starting dose was 35 mg/m2/wk with continuous G-CSF support. The mean DDI was 27.7 mg/m2/wk for all patients. There were two complete responses (CRs) and eight partial responses (PRs) in 40 assessable patients for an overall response rate of 25% (95% confidence interval [CI], 13% to 41%). The median TTP was 13 weeks and median survival time 33 weeks. The dose-limiting toxicity was neutropenia, with dose delay or reduction required in 14 of 27 patients entered at 35 mg/m2. Febrile neutropenia that required hospitalization was unusual (three of 40 patients, 8%). There were no treatment-related deaths. Grade 3/4 thrombocytopenia occurred in nine patients (23%) and 26 patients (65%) required RBC transfusions for anemia. Seven patients (18%) had reversible grade 3/4 nonhematologic complications, primarily related to neurotoxicity. Grade > or = 3 mucositis was absent.
  
  
  CONCLUSIONS
  Concurrent administration of weekly vinoralbine and daily G-CSF is feasible and permits an increase in DDI for vinorelbine of 43% to 76% over that reported in series without growth factor support. The response rate, TTP, and survival data are encouraging for therapy given to heavily pretreated patients with metastatic breast cancer. Vinorelbine is not cross-resistant with paclitaxel and should be considered for further trials in the dose-intensified mode made possible by G-CSF, alone or combined with other agents.
authors.affiliation: Division of Oncology, University of Washington, Seattle 98195-6043, USA. rbl@radonc.washington.edu
authors.forename: R B
authors.initials: RB
authors.lastname: Livingston
authors.forename: G K
authors.initials: GK
authors.lastname: Ellis
authors.forename: J R
authors.initials: JR
authors.lastname: Gralow
authors.forename: M A
authors.initials: MA
authors.lastname: Williams
authors.forename: R
authors.initials: R
authors.lastname: White
authors.forename: C
authors.initials: C
authors.lastname: McGuirt
authors.forename: B B
authors.initials: BB
authors.lastname: Adamkiewicz
authors.forename: C A
authors.initials: CA
authors.lastname: Long
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control; D017239:Paclitaxel / Q000627:therapeutic use*; D011994:Recombinant Proteins; D016879:Salvage Therapy; D016019:Survival Analysis; D017211:Treatment Failure; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077235:Vinorelbine
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D014747:Vinblastine; D017239:Paclitaxel; D000069585:Filgrastim; D000077235:Vinorelbine