Correlation of drug response with the ATP tumorchemosensitivity assay in primary FIGO stage III ovarian cancer.
OBJECTIVE
Our purpose was to: (a) study the in vitro chemosensitivity of primary epithelial ovarian cancer to drug combinations with cisplatin (CDDP), carboplatin (CBDCA), paclitaxel (PTX), epirubicin (EPI), or cyclophosphamide (CTX) utilizing the ATP tumorchemosensitivity assay (ATP-TCA); (b) correlate the test results with clinical response in patients with FIGO stage III ovarian cancer; and (c) analyze the most useful parameters for interpretation of test results.


METHODS
CBDCA/CTX, CBDCA/PTX, CDDP/PTX, and EPI/PTX were tested in 93 fresh human primary epithelial ovarian cancer specimens. Correlations of in vitro drug sensitivity/resistance and clinical response were performed in 38 patients with FIGO stage III disease utilizing Fisher's exact test and by comparison of progression-free (PFS) and overall survival (OS) between those testing as sensitive or resistant. A progression-free interval of more than 12 months following surgery was classified as clinical response. ATP-TCA results were analyzed using the median effective dose, area under the curve, or a defined sensitivity index.


RESULTS
Evaluable test results were achieved in 83 of 93 patients (89%). EPI/PTX had the highest in vitro activity (P < 0.001). In the clinical correlation, 29 of 38 patients (76%) were classified as in vitro sensitive (sensitivity index [SI] <250) and 9 patients as in vitro resistant (SI >250). The SI was superior for interpretation of test results. Patients testing as chemosensitive had a significantly longer mean PFS (28.5 vs 12.6 months, P = 0.033) and OS (46.1 vs 17.6, P = 0.03) compared to those patients predicted to be resistant. The assay demonstrated a sensitivity, specificity, and positive and negative predictive value of 95, 44, 66, and 89%, respectively (Fisher's exact test, P = 0. 007).


CONCLUSIONS
The observed in vitro efficacy of EPI/PTX in primary epithelial ovarian cancer specimens warrants further clinical evaluation. The high evaluability rate and the observed correlation with PFS and OS, within the limitations of a nonrandomized study, support the use of the ATP chemosensitivity assay in future prospective assay-directed trials.
Konecny
G
G
Division of Hematology-Oncology, UCLA School of Medicine, Los Angeles, California 90095-1678, USA.
Crohns
C
C
Pegram
M
M
Felber
M
M
Lude
S
S
Kurbacher
C
C
Cree
I A
IA
Hepp
H
H
Untch
M
M
D000255:Adenosine Triphosphate / Q000097:blood; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D016190:Carboplatin / Q000494:pharmacology; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology*; D002945:Cisplatin / Q000494:pharmacology; D003520:Cyclophosphamide / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D015251:Epirubicin / Q000494:pharmacology; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D017239:Paclitaxel / Q000494:pharmacology; D011237:Predictive Value of Tests; D012044:Regression Analysis; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D015251:Epirubicin; D000255:Adenosine Triphosphate; D003520:Cyclophosphamide; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin