Salvage Chemotherapy with Cisplatin and 5-Fluorouracil in Metastatic Breast Cancer. Particular Activity against Liver Metastases

2012 
Background: The prognosis of patients with metastatic breast cancer who have failed to respond to at least two different chemotherapy regimens is poor. Such patients with metastatic disease to the liver have even worse prognosis. Cisplatin and 5-fluorouracil (5-FU) can be given in patients with impaired hepatic function but their combination has not been extensively studied in this setting. Patients and Methods: We retrospectively collected data from our registry on patients with advanced metastatic breast cancer who received combination of cisplatin/5-FU. We sought to determine the toxicity, the response rate, the disease control rate and the survival of this combination. Results: We identified 25 heavily pre-treated patients, out of which 19 (76%) had liver metastases. They had been treated before with a median of three lines of cytotoxic chemotherapy. The majority of patients had also received hormonal manipulation or trastuzumab. The median number of cisplatin/5-FU administered cycles, without toxic deaths or unexpected toxicities was four. The partial response (PR) rate was 32% and the disease control rate (DCR) was 68%. The time to progression was five months and the median survival after starting on cisplatin/5-FU was six months. Conclusion: The combination of cisplatin/5-FU is active and safe in heavily pre-treated patients with metastatic breast cancer even in the presence of liver metastases and jaundice. The use of taxanes and of dose-dense regimens, as well as the use of aromatase inhibitors and trastuzumab in the adjuvant setting has reduced the rate of breast cancer relapse. The establishment of predictive and prognostic models including the Gail model, mRNA tests (OncotypeDx and Mammaprint) and the recognition of molecular profiles (luminal A and B, HER2+ and triple-negative (TN)) will further optimize adjuvant therapies. In the metastatic breast cancer (MBC) setting, especially in cases of hormone-unresponsive or hormone-refractory disease, the options are limited, and the patients' responses become progressively shorter. This is particularly true for patients who have recently been exposed to adjuvant cytotoxic therapy. The introduction of capecitabine, vinorelbine, gemcitabine, eribulin, ixabepilone, lapatinib and bevacizumab has provided benefits but only limited prolongation of overall survival (OS). Since many cytotoxics are metabolized by or are toxic to the liver, the management of patients with impaired hepatic function is challenging. Cisplatin and 5-fluorouracil (5-FU) can be given with relative safety in the setting of liver dysfunction. In this report we announce our single center experience on the use of cisplatin and 5-FU in the advanced MBC setting. We have used this regimen mostly for patients with liver metastasis or liver dysfunction or as salvage therapy in the very advanced setting.
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