Platinum compounds in the treatment of advanced breast cancer

Abstract

Interest in platinum compounds for the treatment of breast cancer has been reawakened because of preclinical studies indicating synergy of platinum salts with the monoclonal antibody trastuzumab in human breast cancer cell lines that overexpress HER2/neu. Cisplatin, carboplatin, and iproplatin are not very active as single agents in patients with previously treated metastatic breast cancer (MBC). The activity of oxaliplatin has not been adequately tested in refractory MBC. On the other hand, cisplatin is very active as first-line chemotherapy, with response rates (RR) of 50%; carboplatin appears to be moderately active in patients without prior chemotherapy (RR around 30%). The clinical effectiveness of the other platinum compounds (iproplatin, oxaliplatin, and others) has not yet been fully tested as first-line chemotherapy. Platinum compounds have been extensively tested in combination with other antitumoral agents. Cisplatin combinations have been employed as neoadjuvant chemotherapy in women with locally advanced breast cancer. These combinations are very active, although the precise contribution of cisplatin to the overall activity is not known. Combinations with cisplatin have been investigated, essentially, as salvage therapy for patients with previously treated MBC. The combinations of cisplatin with older pharmacological agents (5-fluorouracil, etoposide) have moderate activity, while the combinations of cisplatin with the newer agents (vinorelbine, paclitaxel, docetaxel, gemcitabine) appear to be more active. The combinations of carboplatin with the classical agents (5-fluorouracil, etoposide) are poorly active in previously treated MBC; however, the combination of carboplatin with the taxanes (docetaxel, paclitaxel) is more active. Of greatest interest is the synergy between the platinum derivatives and the monoclonal antibody trastuzumab demonstrated in vitro in breast cancer cell lines overexpressing HER2/neu. Currently, several combinations of platinum compounds (either cisplatin or carboplatin) with docetaxel and trastuzumab are under clinical testing in patients with MBC who overexpress HER2/neu. The preliminary results are very promising, and these combinations will soon be tested in the adjuvant setting. Cisplatin, carboplatin, and perhaps, oxaliplatin appear to have some antitumor activity in MBC and can be combined safely with other agents that are active in this disease. However, the precise role that platinum compounds play in the treatment of breast cancer remains to be defined.