Stordal Britta, Pavlakis Nick, Davey Ross
Bill Walsh Cancer Research Laboratories, Royal North Shore Hospital and University of Sydney, St. Leonards, NSW 2065, Australia.
Cancer Treat Rev. 2007 Jun;33(4):347-57. doi: 10.1016/j.ctrv.2007.01.009. Epub 2007 Mar 23.
Oxaliplatin is widely regarded as being active in cisplatin-resistant cancer. We undertook a systematic review of the literature to identify, describe and critique the clinical and pre-clinical evidence for the use of oxaliplatin in patients with "cisplatin-resistant" cancer. We identified 25 pre-clinical cell models of platinum resistance and 24 clinical trials reporting oxaliplatin based salvage therapy for cisplatin-resistant cancer. The pre-clinical data suggests that there is cross-resistance between cisplatin and oxaliplatin in low-level resistance models. In models with high level resistance (>10-fold) there is less cross-resistance between cisplatin and oxaliplatin, which may be a reason why oxaliplatin is thought to be active in cisplatin-resistant cancer. In clinical trials where oxaliplatin has been used as part of salvage therapy for patients who have failed cisplatin or carboplatin combination chemotherapy, there was a much lower response rate in patients with platinum-refractory or resistant cancers compared to platinum-sensitive cancers. This suggests that there may be cross-resistance between cisplatin and oxaliplatin in the clinic. Oxaliplatin as a single agent had a poor response rate in cisplatin refractory and resistant cancer. Oxaliplatin performed better in combination with other agents for the treatment of platinum-resistant/refractory cancer suggesting that the benefit of oxaliplatin may lie in its more favourable toxicity and ability to be combined with other drugs rather than an underlying activity in cisplatin resistance. Oxaliplatin therefore should not be considered broadly active in cisplatin-resistant cancer.
奥沙利铂被广泛认为对顺铂耐药的癌症具有活性。我们对文献进行了系统综述，以识别、描述和批判使用奥沙利铂治疗“顺铂耐药”癌症患者的临床和临床前证据。我们确定了25个铂耐药的临床前细胞模型和24项报告奥沙利铂用于顺铂耐药癌症挽救治疗的临床试验。临床前数据表明，在低水平耐药模型中，顺铂和奥沙利铂之间存在交叉耐药。在高水平耐药（>10倍）的模型中，顺铂和奥沙利铂之间的交叉耐药较少，这可能是奥沙利铂被认为对顺铂耐药癌症具有活性的一个原因。在奥沙利铂被用作顺铂或卡铂联合化疗失败患者挽救治疗一部分的临床试验中，与铂敏感癌症患者相比，铂难治或耐药癌症患者的缓解率要低得多。这表明在临床中顺铂和奥沙利铂之间可能存在交叉耐药。奥沙利铂作为单一药物在顺铂难治和耐药癌症中的缓解率较低。奥沙利铂与其他药物联合用于治疗铂耐药/难治性癌症时表现更好，这表明奥沙利铂的益处可能在于其更有利的毒性以及与其他药物联合的能力，而不是其在顺铂耐药方面的内在活性。因此，奥沙利铂不应被广泛认为对顺铂耐药癌症具有活性。
