High-dose sequential chemotherapy (HDSC) with peripheral blood progenitor cells (PBPC) support for high-risk breast cancer (BC)

Abstract

11026 Background: Recent reports suggest that intensified adjuvant chemotherapy with stem cell support improve disease free (DFS) and overall survival (OS) in subgroups of patients with high risk BC. We retrospectively analyzed the efficacy, safety and feasibility of a program of HDSC with PBPC support (according to the Milan protocol, ASCO 2001) in patients with BC at high risk of recurrence Methods: Between February 1995 and January 2001, 201 non-consecutive patients with more than 3 positive axillary nodes at surgery, median age 46 (range 27–62), has been evaluated. Median number of involved nodes was 15 (range 3–48), 38% and 49% pts had ER and PgR negative tumors, respectively. Fourty-sevent percent of pts had tumors with a high proliferative activity. HDSC consisted of sequential administration of cyclosphosphamide 7 g/m2 (day 0) plus filgrastim 5 μg/kg s.c. daily and stem cell collection, methotrexate 8 g/m2 plus vincristine 2 mg/m2 (day +16), and two consecutive courses of epidoxorubicin 120 mg/m2 (days +23 and + 38) plus filgrastim 5 μg/kg s.c. daily. Myeloablative therapy (day +58) consisted of thiotepa 600 mg/m2 and melphalan 160 mg/m2 plus PBPCs and filgrastim 5 μg/kg s.c. daily. Results: Three pts discontinued the program permanently because of toxicity. A median of 9,35x106/kg (range 3.35–35.62) CD34+ cells was infused. Engraftment for neutrophils (> 500/μl) and platelets (> 20.000/μl) was observed a median of 9 days (range 7–17) and 10 days (range 7–18) after PBPC infusion, respectively. No treatment-related deaths were recorded. After a median follow-up of 79 months, 108 (54%) pts are disease- free. Ninety-three patients experienced disease recurrence [9/93 (10%) pts had loco regional disease recurrence and 84/93 (90%) pts distant recurrence], of whom 58/93 (63%) have died. Five-year DFS and OS from the start of treatment are 55% and 71%, respectively. No poor marrow function, myelodysplastic syndrome or secondary tumors were observed. In 2-sided log-rank tests, hormone-receptor status and the number of tumor-positive axillary lymph nodes were significant prognostic factors for DFS. Conclusions: Our results confirm that HDSC is a safe procedure and is associated with favorable outcome in patients with high-risk BC. No significant financial relationships to disclose.