Treating Cisplatin-Resistant Cancer: A Systematic Analysis of Oxaliplatin or Paclitaxel Salvage Chemotherapy

Abstract

Objective: To examine the pre-clinical and clinical evidence for the use of oxaliplatin or paclitaxel salvage chemotherapy in patients with cisplatin-resistant cancer. Methods:Medline was searched for 1) Cell models of acquired resistance reporting cisplatin, oxaliplatin and paclitaxel sensitivities and 2) Clinical trials of single agent oxaliplatin or paclitaxel salvage therapy for cisplatin/carboplatin-resistant ovarian cancer. Results: Oxaliplatin -Oxaliplatin is widely regarded as being active in cisplatin-resistant cancer. In contrast, data in cell models suggests that there is crossresistance between cisplatin and oxaliplatin in cellular models with resistance levels which reflect clinical resistance (<10 fold). Oxaliplatin as a single agent had a poor response rate in patients with cisplatin-resistant ovarian cancer (8%, n=91).Oxaliplatin performed better in combination with other agents for the treatment of platinum-resistant 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. Paclitaxel -Cellular data

Micro-RNA149 confers taxane resistance to malignant mesothelioma cells via regulation of P-glycoprotein expression

“…This supports the observation that Cisplatin resistant tumors remain sensitive to Paclitaxel since Cisplatin-induced up-regulation of miRNA149 would down-regulate P-gp maintaining Paclitaxel sensitivity. 42 In conclusion, our results demonstrate miRNA149 directly influences P-gp overexpression supporting the notion that this miRNA is not only a tumor suppressor but also a chemo-modulator. Moreover, the suggested dependence upon how resistance develops makes miRNA149 an ideal candidate for identifying alternative therapeutic interventions and prognostication.…”