DOSE-ESCALATING INDUCTION CHEMOTHERAPY SUPPORTED BY LENOGRASTIM PRECEDING HIGH-DOSE CONSOLIDATION CHEMOTHERAPY FOR ADVANCED BREAST-CANCER - SELECTION OF THE MOST ACCEPTABLE REGIMEN TO INDUCE MAXIMAL TUMOR RESPONSE AND INVESTIGATION OF THE OPTIMAL TIME TO COLLECT PERIPHERAL-BLOOD PROGENITOR CELLS FOR HEMATOLOGICAL RESCUE AFTER HIGH-DOSE CONSOLIDATION CHEMOTHERAPY

Background: In advanced breast cancer high-dose consolidation chemotherapy with haematological rescue has resulted in prolonged disease free and overall survival in a small percentage of patients. Maximal reduction of the tumor burden by intensive induction treatment preceding the high-dose chemotherapy may favor that outcome. The aims of this study were to find rapid highly effective induction regimen with acceptable toxicity and to examine the optimal time for peripheral blood progenitor cell (PBPC) collection for haematological rescue. Subjects and methods: Twenty-four patients received 4 cycles of FAC chemotherapy (5-FU, adriamycin, cyclophosphamide), each followed by 10 mug/kg/d of lenograstim (glycosylated rHuG-CSF) s.c. day 2 to 11. Chemotherapy was administered at 4 dose intensity levels with 6 patients included at each level (level 1:500(F)/50(A)/500(C) mg/m2/3wk, level 2: 500/50/500 mg/m2/2wk, level 3: 500/75/500 mg/m2/2wk, level 4: 500/75/1000 mg/m2/2wk d1 i.v.). In addition lenograstim (10 mug/kg/d s.c.) was administered for a period of 10 days before (period X) and after (period Y) chemotherapy. In 16 patients (4 at each dose intensity level) assessment of PBPC was performed during period X and Y as well as during cycle 1 and 4. A single apheresis to collect PBPC was planned during chemotherapy cycle 1. Results: The best response was obtained at dose intensity level 3 (all 6 patients responded, 3 of them achieved CR) with acceptable toxicity. Peak circulating numbers of total CFC/ml blood were median 5819 (period X), 4635 (cycle 1), 3807 (cycle 4) and 3519 (period Y) and occurred concurrently with peak circulating numbers of CD34+ cells. The PBPC collections contained median 15.2 x 10(4)/kg GM-CFC and median 3.76 x 10(6)/kg CD34+ cells. Three patients received high-dose consolidation chemotherapy with PBPC support. Recovery of ANC > 0.5 x 10(9)/l occurred on median day 11 and of platelets > 20 x 10(9)/l on median day 10. Conclusion: Dose intensity level 3 is the best usable induction regimen in this study. The optimal time for apheresis is either during lenograstim before chemotherapy treatment or during the first cycle of chemotherapy. Rapid haematological recovery was obtained by reinfusion of PBPC as sole source of support in the patients receiving high-dose consolidation chemotherapy.