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 µg/kg was administered daily from day +5 to +10 in order to accelerate hematopoietic recovery, or 48 h 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 × 10⁶/kg CD34+ cells. The median number of CD34+ harvested per patient was 15 × 10⁶/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.