Predicting resistance to platinum-containing chemotherapy with the ATP tumor chemosensitivity assay in primary ovarian cancer.
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.


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.


CONCLUSIONS
ATP-TCA results in combination with the use of IndexSUM > 250 are best able to predict platinum resistance.
Department of Obstetrics and Gynecology, University of Tuebingen, 72076 Tuebingen, Germany. Hans.Neubauer@med.uni-tuebingen.de
Hans
H
Neubauer
Maya
M
Stefanova
Erich
E
Solomayer
Christoph
C
Meisner
Manfred
M
Zwirner
Diethelm
D
Wallwiener
Tanja
T
Fehm
D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016190:Carboplatin / Q000627:therapeutic use*; D002945:Cisplatin / Q000627:therapeutic use*; D004341:Drug Evaluation; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis
D000255:Adenosine Triphosphate; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin