In vitro extreme drug resistance assay to taxanes or platinum compounds for the prediction of clinical outcomes in epithelial ovarian cancer: A prospective cohort study

Purpose: We sought to investigate the efficacy of in vitro extreme drug resistance (EDR) assay for the prediction of drug response, platinum-resistance (progression-free survival, PFS <6 months) and survival in patients with epithelial ovarian cancer (EOC) who received taxane- and platinum-based chemotherapy after surgery. Methods: Between December 2005 and August 2007, 43 patients were enrolled prospectively. They underwent staging laparotomy followed by six or nine cycles of taxane- and platinum-based chemotherapy, and their tumors were submitted for in vitro EDR assay to taxanes (paclitaxel or docetaxel) and platinum compounds (carboplatin or cisplatin). Results: The rates of EDR to taxanes and platinum compounds were 20.9% (9/43) and 23.3% (10/43). Patients with EDR to platinum compounds showed a lower rate of overall response (60 vs. 100%), a higher rate of platinum-resistance (50 vs. 18.2%) and poor overall survival (OS) (median OS; 29.2 vs. 33.7 months) than those without EDR to platinum compounds (P < 0.05), whereas patients with EDR to taxanes showed poor PFS than those without EDR to taxanes (12.5 vs. 19 months, P < 0.01). Moreover, suboptimal debulking surgery and EDR to taxanes were poor prognostic factors for PFS (adjusted hazard ratio 3.215 and 3.984; 95% confidence interval 1.845-7.895 and 3.814-11.674, respectively) although there was no independent risk factor for poor OS by the multivariate Cox's proportional hazard analysis. Conclusions: In vitro EDR assay to taxanes and platinum compounds may be helpful for predicting drug response, platinum-resistance and survival in patients with EOC who received taxane- and platinum-based chemotherapy after staging laparotomy.