title: Dose-dense vinorelbine and paclitaxel with granulocyte colony-stimulating factor in metastatic breast cancer patients: anti-tumor activity and peripheral blood progenitor cell mobilization capability.
abstract: We studied the safety, activity and peripheral blood progenitor cell mobilizing capability of a dose-dense combination of vinorelbine (VNB) and paclitaxel (PTX) as first-line chemotherapy for patients with metastatic breast cancer (MBC). Forty-three MBC patients were submitted to four cycles of VNB 30 mg/m2 and PTX 175 mg/m2 intravenously, every 2 weeks, as the first induction step of a tandem high-dose chemotherapy program. Granulocyte colony-stimulating factor (G-CSF) 5 microg/kg was administered daily from day +5 to +10 in order to accelerate hematopoietic recovery, or 48h after the last VNB-PTX when a leukapheresis was planned (after the third or fourth cycle). A total of 172 cycles were administered. The mean delivered dose-intensity of VNB and PTX was 14.7 and 86 mg/m2/week, respectively (98% of the planned dose-intensity). The main per-patient toxicities were: peripheral neurotoxicity (G1/2 60%, G3 5%), constipation (G1/2 10%), oral mucositis (G1/2 20%), and asthenia (G1/2 35%). Hematological toxicity was unremarkable, except for anemia with hemoglobin (Hb) values < 10 g/dl (28%), and lymphopenia with lymphocyte counts < 1000/mm3 (28%). Two complete (5.1%) and 24 partial (61.5%) responses were observed in 39 assessable patients, for an overall response rate of 66.6% (95% CI 51.6-80.9). A median of one apheretic procedure (range 1-3) was required to achieve the target number of 6 x 10(6)/kg CD34+ cells. The median number of CD34+ harvested per patient was 15 x 10(6)/kg (range 6.4-36.5). Four cycles of dose dense VNB and PTX showed a favorable toxicity profile, a relevant anti-tumor activity and a high peripheral blood progenitor cell mobilizing activity.
authors.affiliation: Dipartimento di Medicina Interna, Università di Genova, Genova, Italy. aballestrero@unige.it
authors.forename: Alberto
authors.initials: A
authors.lastname: Ballestrero
authors.forename: Filippo
authors.initials: F
authors.lastname: Montemurro
authors.forename: Roberta
authors.initials: R
authors.lastname: Gonella
authors.forename: Antonio
authors.initials: A
authors.lastname: Capaldi
authors.forename: Marco
authors.initials: M
authors.lastname: Danova
authors.forename: Daniele
authors.initials: D
authors.lastname: Friedman
authors.forename: Maria
authors.initials: M
authors.lastname: Puglisi
authors.forename: Massimo
authors.initials: M
authors.lastname: Aglietta
authors.forename: Franco
authors.initials: F
authors.lastname: Patrone
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077235:Vinorelbine
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D014747:Vinblastine; D017239:Paclitaxel; D000077235:Vinorelbine