Clinical value of in vitro drug sensitivity testing based on short-term effects on DNA and RNA metabolism in ovarian cancer.
The hypothesis that in vitro chemosensitivity testing could predict clinical outcome was tested in women with ovarian cancer. Short-term drug effects on DNA and RNA metabolism (by inhibition of 3H-thymidine and 3H-uridine incorporation) were measured in primary cultures of tumor cells. In vitro inhibitory effects were found with the four drugs tested: cisplatin, adriamycin, melphalan, and methotrexate. From data based on impaired RNA and/or DNA metabolism (greater than or equal to 20% inhibition), correct prediction of "sensitivity" was 79% and that of "resistance" was 84%. An analysis of the predictive value of both assays, used singly or together, revealed a high specificity but moderate sensitivity; the best positive predictive value (94%) was obtained when both RNA and DNA metabolisms were impaired. Our results support the idea that two subsets of patients who are being considered for cytotoxic chemotherapy can be selected; those who may benefit from treatment and those who may not, regardless of the drugs tested in vitro or used in vivo.
Khoo
S K
SK
Department of Obstetrics and Gynaecology, University of Queensland, Australia.
Hurst
T
T
Webb
M J
MJ
Dickie
G
G
Kearsley
J
J
Parsons
P G
PG
Mackay
E V
EV
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000187:drug effects*; D004317:Doxorubicin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008558:Melphalan / Q000494:pharmacology; D008727:Methotrexate / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics; D012334:RNA, Neoplasm / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D012334:RNA, Neoplasm; D004317:Doxorubicin; D002945:Cisplatin; D008558:Melphalan; D008727:Methotrexate