Platinum compounds in the treatment of advanced breast cancer.
Platinum compounds in the treatment of advanced breast cancer.
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DOI：
10.3816/cbc.2001.n.022
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发表时间：
2001-10-01
影响因子：
3.1
通讯作者：
Martin, M
中科院分区：
文献类型：
--
作者：
Martin, M
由于临床前研究表明铂盐与单克隆抗体曲妥珠单抗在过表达HER 2/neu的人乳腺癌细胞系中具有协同作用，因此重新唤起了对铂化合物治疗乳腺癌的兴趣。顺铂、卡铂和异丙铂作为单药在既往接受过治疗的转移性乳腺癌（MBC）患者中的活性不高。尚未在难治性MBC中充分检测奥沙利铂的活性。另一方面，顺铂作为一线化疗非常活跃，缓解率（RR）为50%;卡铂在既往未接受化疗的患者中似乎具有中度活性（RR约为30%）。其他铂类化合物（异丙铂、奥沙利铂等）作为一线化疗的临床有效性尚未得到充分检验。铂化合物已被广泛测试与其他抗肿瘤药物的组合。顺铂组合已被用作局部晚期乳腺癌妇女的新辅助化疗。这些组合是非常活跃的，尽管顺铂对总体活性的精确贡献尚不清楚。与顺铂的组合已被研究，基本上，作为挽救治疗的患者与先前治疗的MBC。顺铂与较老的药理学药物（5-氟尿嘧啶、依托泊苷）的组合具有中等活性，而顺铂与较新的药物（长春瑞滨、紫杉醇、多西他赛、吉西他滨）的组合似乎更有活性。卡铂与经典药物（5-氟尿嘧啶，依托泊苷）的组合在先前治疗的MBC中活性较差;然而，卡铂与紫杉烷类（多西他赛，紫杉醇）的组合活性更高。最令人感兴趣的是铂衍生物和单克隆抗体曲妥珠单抗之间的协同作用，在体外过表达HER 2/neu的乳腺癌细胞系中得到证实。目前，铂化合物（顺铂或卡铂）与多西他赛和曲妥珠单抗的几种组合正在过表达HER 2/neu的MBC患者中进行临床试验。初步结果是非常有希望的，这些组合将很快在佐剂环境中进行测试。顺铂，卡铂，也许，奥沙利铂似乎在MBC中具有一定的抗肿瘤活性，并且可以安全地与其他对这种疾病有活性的药物联合使用。然而，铂化合物在乳腺癌治疗中的确切作用仍有待确定。
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.