Oxaliplatin for the treatment of cisplatin-resistant cancer: A systematic review

Oxaliplatin is widely regarded as being active in cisplati n -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 "cisptati n -resistant" cancer. We identified 25 pre-clinical cell models of platinum resistance and 24 clinical. trials reporting oxaliplatin based salvage therapy for cisplati n- 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 oxaliptatin is thought to be active in cisplati n -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 ptatinum-refractory or resistant cancers compared to platinum-sensitive cancers. This suggests that there may be c ross-resistance between cisplatin and oxaliplatin in the clinic. Oxatiplatin as a single agent had a poor response rate in cis-platin 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 tie in its more favourable toxicity and ability to be combined with other drugs rather than an underlying activity in cisplatin resistance. Oxaliptatin therefore should not be considered broadly active in cisplati n -resistant cancer. Crown Copyright (C) 2007 Published by ELsevier Ltd. All rights reserved.