A systematic review of platinum and taxane resistance from bench to clinic: An inverse relationship

Abstract

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.

Down‐regulated expression of miR‐134 contributes to paclitaxel resistance in human ovarian cancer cells

“…Although initial treatment is successful for 80-90% of the patients, most responders eventually become resistant to a broad range of chemotherapeutic agents thus chemoresistance is one of the most significant obstacles to the successful treatment of ovarian cancer [20].…”

Carboplatin and taxol resistance develops more rapidly in functional BRCA1 compared to dysfunctional BRCA1 ovarian cancer cells

“…A systematic review of the literature by (Stordal et al 2007) revealed that the majority (80%) of cellular models with acquired platinum or taxane resistance displayed an inverse resistance relationship, that is collateral sensitivity to the other agent. A subsequent systematic review by (Stordal et al 2009), revealed that BRCA1 was the mostly likely genetic player in this relationship.…”

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

“…What was unexpected was platinum-resistant patients who have previously received paclitaxel therapy responded better to single agent paclitaxel (RR 35.3% n = 232) than the paclitaxel naïve patients (RR 22.7% n = 1918) (p <0.01 Chi-squared) (Figure 3) (6). Both cohorts of patients had very similar age, performance status, FIGO stage, and number of cycles of prior chemotherapy, there was a difference in histology but this did not account for this difference in response rates (6). Usually if patients have received a drug and experienced disease progression, they are less likely to respond to therapy with a subsequent exposure to the same drug.…”

“…The literature search for models of acquired resistance which report cross resistance data for both cisplatin and paclitaxel identified 137 cell lines (6). For each cell line the fold paclitaxel resistance was plotted against the fold cisplatin resistance, allowing an analysis of the pattern of cross resistance between the two compounds (Figure 2A).…”