Cisplatin Paclitaxel Carboplatin Docetaxel Ovarian Cancer
Stordal, B., Pavlakis, N. and Davey, R., A systematic review of platinum and taxane resitance from bench to clinic: An inverse relationship., Cancer Treatment Reviews, 33, 2007, 688 - 703
Cancer Treatment Reviews;33
We undertook a systematic review of the pre-clinical and clinical literature for studies
investigating the relationship between platinum and taxane resistance. Medline was
searched for 1) cell models of acquired drug resistance reporting platinum and taxane
sensitivities and 2) clinical trials of platinum or taxane salvage therapy in ovarian cancer.
137 models of acquired drug resistance were identified. 68.1% of cisplatin-resistant cells
were sensitive to paclitaxel and 66.7% of paclitaxel-resistant cells were sensitive to
cisplatin. A similar inverse pattern was observed for cisplatin vs docetaxel, carboplatin vs
paclitaxel and carboplatin vs docetaxel. These associations were independent of cancer
type, agents used to develop resistance and reported mechanisms of resistance. 65 eligible
clinical trials of paclitaxel-based salvage after platinum therapy were identified. Studies
of single agent paclitaxel in platinum-resistant ovarian cancer where patients had
previously recieved paclitaxel had a pooled response rate of 35.3% n=232, compared to
22% in paclitaxel naïve patients n=1918 (p<0.01 Chi-squared). Suggesting that pretreatment
with paclitaxel may improve the response of salvage paclitaxel therapy. The
response rate to paclitaxel/platinum combination regimens in platinum-sensitive ovarian
cancer was 79.5% n=88 compared to 49.4% n=85 for paclitaxel combined with other
agents (p<0.001 Chi-squared), suggesting a positive interaction between taxanes and
platinum. Therefore the inverse relationship between platinum and taxanes resistance
seen in cell models is mirrored in the clinical response to these agents in ovarian cancer.
An understanding of the cellular and molecular mechanisms responsible would be
valuable in predicting response to salvage chemotherapy and may identify new
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