ABSTRACT
This study evaluates the in vitro sensitivities of 42 ovarian cancer specimens to the new anticancer agent Paclitaxel (taxol, Tx), cisplatin (DDP), and the combination Tx-DDP with the adenosine triphosphate cell viability assay (ATP-CVA). In vitro response is defined by > or = 50% ATP decrease compared to untreated controls 6-7 days after drug treatment with 20% of the peak plasma concentration (PPC). Response rates were 12% to Tx, 19% to DDP, and 27% to Tx + DDP. The mean IC50's of Tx, DDP, and the combination Tx-DDP were (2.6x, 1.0x, and 0.38x PPC, respectively). The mean inhibition of cell viability was significantly greater with drug combinations compared to single drugs. In 7/11 tumors synergistic effects and in 2/11 additive effects were found between Tx and DDP. We conclude that based on ATP-CVA in vitro results, Tx-DDP shows significantly better activity compared to each of the single drugs in ovarian cancer.
Subject(s)
Adenosine Triphosphate/analysis , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Cisplatin/pharmacology , Ovarian Neoplasms/drug therapy , Paclitaxel/pharmacology , Adenosine Triphosphate/antagonists & inhibitors , Cell Survival/drug effects , Cisplatin/administration & dosage , Drug Screening Assays, Antitumor , Female , Humans , Ovarian Neoplasms/metabolism , Paclitaxel/administration & dosageABSTRACT
The in vitro effects of paclitaxel (Tx) and docetaxel (Taxotere, Txt) are compared in this study using the adenosine triphosphate cell viability assay (ATP-CVA) in 14 cancer cell lines. Eleven cell lines were sensitive and three were partially sensitive to paclitaxel. Nine cell lines were sensitive, three were partially sensitive and two were resistant to docetaxel. Mean IC50s were 3.7-660 ng/ml paclitaxel and 5.4-540 ng/ml docetaxel. In five sensitive cancer cell lines docetaxel was more active than paclitaxel, and in six sensitive cell lines paclitaxel was more active than docetaxel on a concentration basis. Two cell lines were sensitive to paclitaxel and resistant to docetaxel. In one cell line the two compounds had similar activities. In the ATP-CVA, paclitaxel and docetaxel are very active and are partially non-cross-resistant.
