Metronomic cyclophosphamide and capecitabine combined with lapatinib in heavily pretreated metastatic breast cancer (MBC) HER2-positive patients.

Abstract

e11071 Background: Current therapeutic goals for MBC, as an incurable disease, are symptoms and prolonged disease control together with good quality of life. Metronomic chemotherapy has shown efficacy in patients with metastatic breast cancer. We evaluated the efficacy and tolerability of the combination of anti-angiogenetic activity of metronomic chemotherapy with a tyrosine kinase inhibitor such as lapatinib in heavily pre-treated MBC HER-2 positive patients. Methods: Metastatic breast cancer patients HER-2 positive with CEA or Ca15.3 elevated, measurable disease, prior systemic therapy (chemotherapy and/or hormonal therapy) for advanced disease, ECOG performance status < 1 and life expectancy longer than 3 months. MBC patients were treated with metronomic oral capecitabine (1500 mg daily) and cyclophosphamide (50 mg daily) plus lapatinib (1250 mg daily). The treatment was given until disease progression or unacceptable toxicity. Primary objective was time to progression (TTP) and safety. Results: Tenpatients were included. Median age was 56 years old (range 46-76). Median number of previous chemotherapy lines was 5 (range 2-10). Median time to tumor progression was 4 months (2-7). No complete response was observed. Six out of ten patients (60%) with pre-existing only bone metastases achieved a stable disease and/or partial response and are still on treatment after 6 month of therapy. At the same time 100% of these patients exhibited reduction of serum marker concentrations to normal range. No grade 3-4 toxicity was reported. There was no decline in cardiac function. Hematological and gastro-intestinal toxicity was well tolerated (G1-2). No reduction of dose was needed. Conclusions: The treatment appears to be an effective and less toxic option in heavily pretreated MBC patients. Of note is the observed activity in patients with exclusive bone metastases. Monitoring of CEA and Ca15.3 during the first two months of treatment appears to provide a sensitive and economical means of identifying those patients who are responding to the therapy. Therefore, the combination of lapatinib with metronomic chemotherapy should be explored in advance for osseous MBC.