Carmustine-methotrexate combination in breast cancer patients presenting with brain metastases.

Abstract

Abstract Abstract #6119 Purpose: There is currently no standard chemotherapy regimen for breast cancer (BC) patients presenting with brain metastases (BM). Since 1999, in our institution, these patients are treated with an association of carmustine (BCNU) and methotrexate (MTX). We report here the efficacy and safety profile of this association. Patients and methods: In this study, BC patients presenting with BM were treated by an association of BCNU 100 mg/m² on day 1 and MTX 600 mg/m² on day 1 and 15 of a 28 days cycle. Treatment was continued until progression or unacceptable toxicity. In order to evaluate this combination, we analyzed activity by recording tumor response rates, progression-free survival (PFS) and overall survival (OS), treatment compliance by analyzing Relative Dose Intensity (RDI) and safety by analyzing clinical and biological toxicities using NCI CTCAE v3.0. Results: Fifty patients were treated between 1999 and 2007, with a median age of 52 years (range 26-77 years). Median time between diagnosis of BC and BM was 37 months (0-180). One patient had synchronous BM. No tumor was recorded to be Scarf, Bloom and Richardson grade I, 40% were hormonal receptor negative and 50% of the 36 tumors analyzed for HER-2 amplification were positive. 94% of the patients presented with concomitant extra-cerebral disease, mainly bone (76%), liver (46%), lung (42%) and lymph node (26%) metastases. The number of previous chemotherapy regimens in the metastatic setting was 2 (1-5). The median number of administered cycles of BCNU-MTX was 3 (1-20). 30% of the patients received up to 6 chemotherapy cycles, with 20% patients continuing the treatment after 6 cycles. There were 11 objective responses (23% [IC95% 12-37]) among 48 evaluable patients, with an additional 29% disease stabilization, for a total 52% of patients with clinical benefit. Median PFS and OS were 4.2 (95%CI: 2.8-5.3) and 6.9 (4.2-10.7) months respectively, with a one-year OS rate of 32% (20-46). There were 2 presumed treatment-related deaths. The median RDI for BCNU and MTX were 0.98 (0.31-1.1) and 0.96 (0.57-1.66) respectively. Treatment was well tolerated, with the most common grade 3-4 toxicities per patients as follow (%pts): anemia (8.4), neutropenia (40.4), thrombocytopenia (21.2), and grade 3 fatigue (10.6). One patient developed febrile neutropenia. Poor prognosis was associated with a poor performance status in a univariate analysis of OS.Conclusion: In this population of heavily pretreated patients affected by BM from BC, the combination of BCNU-MTX appears to be an effective and well tolerated combination in good performance status BC patients presenting with BM. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6119.