Conservation of in vitro drug resistance patterns in epithelial ovarian carcinoma.
OBJECTIVE
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.
Tewari
Krishnansu S
KS
The Division of Gynecologic Oncology, The Chao Family Comprehensive Cancer Center, University of California, Irvine-Medical Center, 101 The City Drive, Orange, CA 92868, USA.
Mehta
Rita S
RS
Burger
Robert A
RA
Yu
Ing-Ru
IR
Kyshtoobayeva
Ainura S
AS
Monk
Bradley J
BJ
Manetta
Alberto
A
Berman
Michael L
ML
Disaia
Philip J
PJ
Fruehauf
John P
JP
D002945:Cisplatin / Q000494:pharmacology; D003520:Cyclophosphamide / Q000031:analogs & derivatives / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D009362:Neoplasm Metastasis; D009378:Neoplasms, Multiple Primary / Q000188:drug therapy / Q000473:pathology; D016609:Neoplasms, Second Primary / Q000188:drug therapy / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology; D019772:Topotecan / Q000494:pharmacology
C012358:4-hydroxycyclophosphamide; D019772:Topotecan; D003520:Cyclophosphamide; D017239:Paclitaxel; D002945:Cisplatin