Systemic high-dose intravenous methotrexate in patients with central nervous system metastatic breast cancer.

BACKGROUND: Infusion of high-dose intravenous methotrexate (MTX) has been demonstrating to penetrate the blood-brain barrier. The aim of this present study was to assess the efficacy and safety of high dose MTX in patients with central nervous system (CNS) metastases of breast cancer. METHODS: Twenty-two patients with CNS metastases treated by MTX (3 g/m2) between April 2004 and October 2009 were enrolled. Clinical response rate, time to progression (TTP), overall survival (OS), and safety were assessed. RESULTS: In terms of brain metastases, 2 patients (9%) achieved a partial response, 10 patients (45%) had disease stabilization, and 10 patients (45%) had disease progression. In others metastatic sites, 7 patients (39%) achieved a disease stabilization, and 11 patients (61%) had disease progression. TTP and OS were 2.1 (95%CI 1.4-2.9) and 6.3 (95%CI 1.8-10) months, respectively. CONCLUSION: High-dose MTX demonstrated a moderate activity at 3 g/m2. Nonetheless, the favorable toxicity profile should suggest the possibility to increase the dosage and further study are planned.

[Neoadjuvant before surgery treatments: state of the art in prostate cancer]. / Traitements néoadjuvants préopératoires : mise au point dans le cancer de la prostate.

GOAL: To study the impact of systemic treatment in neoadjuvant strategy before surgery in prostate cancer. MATERIALS: Literature reviews with data analysis from PubMed search using the keywords "neoadjuvant", "chemotherapy", "hormonal therapy", "prostate surgery", "radical prostatectomy", but also reports from ASCO and ESMO conferences. The articles on neoadjuvant treatment before radiotherapy were excluded. RESULTS: First studies with former therapy are more than 15-years-old and with questionable methodology: lack of power to have a clear idea of the impact on survival criteria such as overall survival or relapse-free survival. However, the impact of neoadjuvant hormone therapy on the classic risk factors for relapse (positive margins, intraprostatic disease, positive lymph nodes) was demonstrated by these studies and a Cochrane meta-analysis. The association with hormone therapy seems mandatory in comparison to treatment based solely on chemotherapy and/or targeted therapy. Promising data on the use of new drugs and their combinations arise: abiraterone acetate combined with LHRH analogue showed a fast PSA decrease and higher rates of pathologic complete response. Other results are promising with hormonal blockages at various key points. CONCLUSION: Studies with 2nd generation anti-androgene agents or enzyme inhibitors seem to show very promising results. To provide answers about the effectiveness of current neoadjuvant strategy in terms of survival, other studies are needed: randomized phase III or phase II exploring predictive biomarkers. The design of such trials requires a multidisciplinary approach with urologists, oncologists, radiologists and methodologists.