Conservation of in vitro drug resistance patterns in epithelial ovarian carcinoma

Abstract

Purpose. To compare the in vitro drug resistance profiles of advanced stage primary and recurrent epithelial ovarian cancer specimens using the tritiated thymidine uptake assay.Methods. Extreme drug resistance (EDR) to cisplatin, paclitaxel, 4-hydroxycyclophosphamide, and topotecan was determined for an unselected population of primary and metastatic malignant ovarian tissues, synchronous tumors (primary and metastatic tissues obtained from the same patient at diagnosis), and metachronous lesions (specimens from the same patient before and after chemotherapy).Results. For the large unselected population of malignant tissues (total, N = 6990; primary ovarian, N = 2031; metastatic ovarian, N = 4959), no statistically significant differences were discovered between primary tissues and metastatic lesions when a comparison was made between the percentage of tumors from each group that exhibited extreme drug resistance to the agents assayed. From the library of 6990 specimens, 119 synchronous pairings were identified. These synchronous lesions did not differ significantly in the %EDR between primary and metastatic sites in the same patient; approximately 10% shifted between low drug resistance and EDR. A total of 334 metachronous pairings were identified and the percentage of tissues that exhibited EDR also failed to show a significant difference when primary tumors were compared with matched recurrences in the same patient.Conclusions. For the agents studied, acquired resistance was not a function of disease site. In vitro drug resistance observed at recurrence was not influenced significantly by intervening therapy. It is possible that assay results at diagnosis could be used to guide subsequent therapy at relapse, especially when recurrent tissue is not available for analysis. D

Chemotherapy Resistance as a Predictor of Progression-Free Survival in Ovarian Cancer Patients Treated with Neoadjuvant Chemotherapy and Surgical Cytoreduction Followed by Intraperitoneal Chemotherapy: A Southwest Oncology Group Study

“…Holloway et al [13 ]reported that women who were treated with agents falling into the EDR category on the basis of in vitro testing had significantly inferior survival compared with women who received agents that showed low drug resistance in vitro. Another study of 119 paired synchronous samples of epithelial ovarian cancer found congruent results for EDR in 89% of cases [14]. Loizzi et al [15] demonstrated a significant survival advantage for ovarian cancer patients who were treated with assay-assisted therapy as compared to empiric treatment.…”

Increased paclitaxel resistance in recurrent epithelial ovarian cancer: analysis of metachronous tumors

“…Whether or not ovarian cancer exhibits tumor heterogeneity before and after chemotherapy, demonstrated in an in vitro drug resistance assay, seems to remain controversial [1][2][3][4]. In the largest analysis of an unselected population with ovarian cancer, there was no significant difference in the proportion of extreme drug resistance (EDR) between primary and recurrent cases [1].…”

Predicting platinum resistance in primary advanced ovarian cancer patients with an in vitro resistance index

“…Previous studies by our group demonstrated 25% variation in DNA ploidy between samples from primary tumor and metastases [20], and tumor heterogeneity has been demonstrated between primary tumor and metastatic samples [21] as well as between primary tumor and samples in recurrent OC [22]. In contrast, Tewari et al [23] found no signiWcant diVerence between in vitro drug resistance in primary and metastatic OC lesions, or primary tumors and recurrent samples. Some studies did not report biopsy sites and report inconsistent conclusions [13,24,25].…”

“…This suggests that chemotherapy exposure induces in vitro platinum resistance. Previous studies comparing in vitro resistance between samples obtained before and after chemotherapy exposure show inconsistent results [23,24]. In the present study, the amount of residual tumor after surgery may have inXuenced the results as patients unlikely to achieve optimal debulking was selected for neoadjuvant chemotherapy.…”