• A Gonçalves, A C Braud, F Viret, C Tarpin, E Charaffe-Jauffret, J Jacquemier, D Maraninchi, and P Viens.
• Department of Medical Oncology, Institut Paoli-Calmettes, 13273 Marseille Cedex 9, France. goncalvesa@marseille.fnclcc.fr
• Anticancer Res. 2005 Jan 1; 25 (1B): 663-7.

BackgroundERBB2 overexpression predicts a worse outcome for patients receiving high-dose chemotherapy (HDC). Trastuzumab improves response rate and survival in ERBB2 overexpressing metastatic breast cancer patients (MBC). We investigated the feasibility of combining high-dose alkylating agents with autologous hematopoietic stem cell (AHSC) support and trastuzumab in ERBB2 overexpressing MBC.Patients And MethodsEleven consecutive patients with pre-treated ERBB2 overexpressing MBC were enrolled. HDC regimen consisted of a single course of cyclophosphamide 120 mg/kg + melphalan 140 mg/m2 (CyMEL, n =8), a single course of Thiotepa 600 mg/m2 (TTP, n = 1) or a sequential combination of Thiotepa 600 mg/m2 followed on day 21 by BCNU 600 mg/m2 (TTP-BCNU, n =2). Trastuzumab (4mg/kg) was started 24 h after AHSC infusion and then administered weekly (2 mg/kg).ResultsMedian time to neutrophil and platelet recovery was 10 and 14.5 days, respectively. Three patients experienced febrile neutropenia and in 2 Herpes virus infections were documented. Five grade III/IV mucositis/oesophagitis were recorded. One patient experienced a reversible atrial arrhythmia on day 2 of trastuzumab, and another patients had a nonsymptomatic decrease in LVEF >10% on week 12 of trastuzumab. No toxic death was recorded. Median time to progression was 5 months (1 to 38 +).ConclusionCombining alkylating agent-based HDC and trastuzumab appears to be feasible in ERBB2 overexpressing MBC and warrants further investigation in a larger cohort.

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