Abstract
Background: Preliminary data from phase III randomized studies have failed to show benefit of HDC given as consolidation after anthracycline and alkylating-based chemotherapy in metastatic breast cancer (MBC). Moderate activity of induction regimens and selection of chemoresistant clones are among the possible reasons for these disappointing results. We therefore have designed a phase II study where high-dose alkylating agents are given as consolidation after an induction treatment including the most active agents (epirubicin and paclitaxel) without alkylating agents. Patients and methods: Patients with MBC not previously treated with chemotherapy for metastatic disease were eligible. After six courses of epirubicin-paclitaxel±gemcitabine patients received a course of thiotepa 600 mg/m2 + melphalan 160 mg m2 with hemopoietic support. Pharmacokinetic parameters of thiotepa and melphalan were measured and related to treatment outcomes. The L-VEF of the patients was monitored before and after treatment. Results: Forty-eight patients have been treated. Before HDC 14 patients were in CR, and 34 in PR. A median of 6.92 × 106 (range 1.53-16.6) CD34+ cells/kg were reinfused after HDC. Median days (range) to neutrophils > 0.5 × 109/l and platelets > 20,000 × 109/l were 9.5 (9-33) and 10 days (9-32), respectively. Symptomatic CHF was observed in two patients (4.1%). Cmax and AUC of thiotepa showed a linear relationship with time to progression (TTP) and overall survival (OS): r2=0.6. After HDC the conversion rate from PR to CR was 44.1%. At five years progression-free and overall survival rates are 37.5% and 65%, respectively. A treatment-related death was observed. Conclusions: High-dose thiotepa and melphalan after an epirubicin-paclitaxel-containing treatment is feasible, devoid of significant cardiotoxicity and very active. Pharmacokinetic parameters of high-dose thiotepa might be linked to treatment outcome.
Original language | English |
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Pages (from-to) | 69-74 |
Number of pages | 6 |
Journal | Annals of Oncology |
Volume | 12 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2001 |
Keywords
- High-dose chemotherapy
- Metastatic breast cancer
- Paclitaxel
ASJC Scopus subject areas
- Oncology
- Cancer Research