Predicting resistance to platinum-containing chemotherapy with the ATP tumor chemosensitivity assay in primary ovarian cancer
Neubauer, H.; Stefanova, M.; Solomayer, E.; Meisner, C.; Zwirner, M.; Wallwiener, D.; Fehm, T.
Anticancer Research 28(2a): 949-955
2008
ISSN/ISBN: 0250-7005 PMID: 18507041 Document Number: 616335
Background: Most patients with primary epithelial ovarian cancer (PEOC) treated with carboplatin/paclitaxel will relapse between one to two years. Our purpose was to define the optimal calculation method for the adenosine triphosphate-tumor chemosensitivity assay (ATP-TCA) applied to PEOC treated with platinum-containing chemotherapy and to analyze its predictive relevance. Materials and Methods: ATP-TCA results from 80 PEOC specimens were analyzed applying three different methods: 50% inhibition concentration, sensitivity index (IndexSUM), and area under curve by testing multiple cut-off levels. Correlation between in vitro results and clinical outcome was performed for 61 (76%) patients by univariative and multivariative analysis. Tumor recurrence 6 months after chemotherapy was classified as platinum-resistance. Results: The IndexSUM set at >250 had the highest test sensitivity, specificity, positive and negative predictive value of 90%, 43%, 62% and 81%, respectively. Patients whose tumors were shown to be resistant by ATP-TCA had a higher risk for recurrence (RR) compared to those who tested as sensitive (p<0.003, RR=3.3, 95% CI=1.2-9.4). This result was confirmed after adjustment for FIGO stage by logistic regression (p < 0.004, Odds ratio=8.3, 95% CI=1.9-35.5). In multivariate analysis ATP-TCA and the FIGO-stage were independent predictive factors of early recurrence. Conclusion: ATP-TCA results in combination with the use of IndexSUM >250 are best able to predict platinum resistance.