Extreme Drug Resistance Assay and Response to Chemotherapy in Patients with Epithelial Ovarian Cancer
Abstract & Commentary
Eltabbakh and colleagues have recently reported a study of the extreme drug resistance (EDR) assay, the purpose of which was to correlate the results of the EDR assay to response to first-line paclitaxel/cisplatin chemotherapy among patients with epithelial ovarian cancer. Seventy-five patients for whom the assay was performed on tissue from primary surgery and who were then treated with paclitaxel/cisplatin chemotherapy were the principal focus of this study. The prevalence of EDR to paclitaxel was 20% (n = 15) and to cisplatin it was 2.7% (n = 2). Only one patient exhibited EDR to both paclitaxel and cisplatin. Neither the overall response rate (86.4% vs 81.3%) nor the surgical response rate (25.4% vs 12.5%) differed significantly between patients whose tumors demonstrated no EDR to either paclitaxel or cisplatin and those whose tumors demonstrated EDR to at least one of these two drugs. The single patient whose tumor exhibited EDR to both paclitaxel and cisplatin had tumor progression. The sensitivity, specificity, positive predictive value, and negative predictive value of the EDR assay were 79.6%, 27.0%, 86.0%, and 19.0%, respectively. Eltabbakh et al conclude that EDR to paclitaxel does not preclude response to the combination of paclitaxel and cisplatin as primary therapy for patients with epithelial ovarian cancer, and that the role of the EDR assay in the primary management of patients with this cancer remains to be determined. (Eltabbakh GH, et al. Gynecol Oncol 1998;70:392-397.)
Comment by David M. Gershenson, MD
The oncology community longs for a reliable in vitro test that predicts response (or lack of response) to chemotherapy. Such a test would allow us to better select patients for chemotherapy who would benefit. In addition, it would avoid unnecessary, expensive, potentially toxic treatment for a large number of patients. Several different assays have enjoyed popularity over the past two decades or so, but none has clearly emerged as the best option. Within the gynecologic oncology community today, the Oncotech assay—the one used in the present study—is the most popular. It is marketed to predict drug resistance, not drug sensitivity. Unfortunately, in my opinion, there is not sufficient evidence to support its routine use. The study, although admirable in its intent, has insufficient patient numbers to answer the question. As Eltabbakh et al note, only one patient’s tumor demonstrated EDR to both paclitaxel and cisplatin, and that patient progressed on treatment. Resistance to only one of two drugs has little use in patients receiving combination chemotherapy. In addition, with limited choices for first-line therapy, one could argue that such an assay would be more useful in the refractory setting. In fact, we are initiating a multicenter trial for patients with recurrent ovarian cancer in which patients undergo fine needle aspiration of metastatic tumor. The cells are then tested using the EDR assay. Patients are then randomized into one of two arms: 1) assay-directed treatment using one of three drugs to which the tumor is least resistant; and 2) non-assay-directed treatment in which patients are simply randomized again to one of the same three drugs. Of course, any in vitro assay is potentially plagued by the phenomenon of tumor heterogeneity.
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