Chemotherapy time interval and development of platinum and taxane resistance in ovarian, fallopian, and peritoneal carcinomas

Abstract

To evaluate drug resistance after exposure to neoadjuvant chemotherapy and to postoperative chemotherapy in epithelial ovarian, fallopian, and primary peritoneal carcinomas. In vitro drug resistance assay results (EDR Assay, Oncotech, Inc.) for platinum and taxane were evaluated for the following three groups: (1) primary cytoreductive surgery without prior chemotherapy; (2) primary cytoreductive surgery after neoadjuvant chemotherapy with platinum and taxane; and (3) recurrent cases after postoperative chemotherapy with platinum and taxane. Proportions of extreme drug resistance (EDR) were analyzed with Fisher's exact test. There were 277 cases that underwent primary cytoreductive surgery without prior chemotherapy: 14 cases of primary cytoreductive surgery after neoadjuvant chemotherapy with platinum and taxane, and 65 recurrent cases. Primary cytoreductive cases following neoadjuvant chemotherapy displayed an increased proportion of EDR to platinum agents compared to primary cytoreductive surgery without prior chemotherapy: neoadjuvant versus non-neoadjuvant, cisplatin 30 versus 7.3%, OR 5.4, 95%CI 1.3-23.2, P=0.027; carboplatin 33.3 versus 9.2%, OR 4.9, 95%CI 1.4-17.6, P=0.038. There were no differences in the proportion of EDR to taxanes between the two groups. On the contrary, recurrent cases showed an increased proportion of EDR to paclitaxel compared to primary cytoreductive surgery without prior chemotherapy: recurrent versus primary, paclitaxel 33.3 versus 21.1%, OR 1.9, 95%CI 1.0-3.5, P=0.031. There were no differences in the proportion of EDR for platinum and docetaxel between the two groups. Among recurrent cases, there was statistical significance between proportion of paclitaxel EDR and time interval of initial and recurrent surgeries (R2 0.143, P=0.011). Recurrent surgery after 5 years from initial cytoreduction was significantly associated with increased proportion of EDR to paclitaxel: 61.5 versus 22.6%, OR 5.5, 95%CI 1.35-22.2, P=0.011. Platinum resistance was common after neoadjuvant chemotherapy, while paclitaxel resistance was common after postoperative chemotherapy.