Abstract
The objective of this study was to examine the preclinical and clinical evidence for the use of oxaliplatin or paclitaxel salvage chemotherapy in patients with cisplatin-resistant cancer.
Medline was searched for (a) cell models of acquired resistance, reporting cisplatin, oxaliplatin, and paclitaxel sensitivities; and (b) clinical trials of single-agent oxaliplatin or paclitaxel salvage therapy for cisplatin/carboplatin-resistant ovarian cancer. Oxaliplatin is widely regarded as being active in cisplatin-resistant cancer. In contrast, data in cell models suggests that there is cross-resistance between cis-platin and oxaliplatin in cellular models with resistance levels that reflect clinical resistance (less than tenfold). Oxaliplatin, as a single agent, had a poor response rate in patients with cisplatin-resistant ovarian cancer (8%, n = 91). In the treatment of platinum-resistant cancer, oxaliplatin performed better in combination with other agents, suggesting that the benefit of oxaliplatin may lie in its more favorable toxicity and its 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.
Cellular data suggest that paclitaxel is active in cisplatin-resistant cancer. 68.1% of cisplatin-resistant cells were sensitive to paclitaxel. As a single agent, paclitaxel had a response rate of 22% in patients with platinum-resistant ovarian cancer (n = 1,918), a significant increase from the response of oxaliplatin (p < 0.01). Paclitaxel-resistant cells were also sensitive to cisplatin, suggesting that alternating between agents may be beneficial. Studies of single-agent paclitaxel in platinum-resistant ovarian cancers where patients had previously received paclitaxel had an improved response rate of 35.3% n = 232 (p < 0.01), suggesting that pretreatment with paclitaxel improves the response of salvage paclitaxel therapy.
Cellular models reflect the resistance observed in the clinical treatment of ovarian cancer, as the cross-resistant agent oxaliplatin has a lower response rate compared to the non-cross-resistant agent paclitaxel. Alternating therapy with cisplatin and paclit-axel may therefore lead to an improved response rate in ovarian cancer.
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Stordal, B., Pavlakis, N., Davey, R. (2009). Treating Cisplatin-Resistant Cancer: A Systematic Analysis of Oxaliplatin or Paclitaxel Salvage Chemotherapy. In: Bonetti, A., Leone, R., Muggia, F.M., Howell, S.B. (eds) Platinum and Other Heavy Metal Compounds in Cancer Chemotherapy. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-459-3_27
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