Clinical value of in vitro drug sensitivity testing based on short-term effects on DNA and RNA metabolism in ovarian cancer.

Abstract

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.