Combination chemotherapy tested in a short-term thymidine incorporation assay in primary cultures of ovarian adenocarcinomas.
Fifty-six tumor specimens from patients with ovarian adenocarcinoma were tested for sensitivity to single and combination drug regimens in a short-term antimetabolic assay measuring inhibition of thymidine incorporation. Response in primary cultures to drug combinations was compared with response to each component drug: cisplatinum, chlorambucil, adriamycin, etoposide and activated cyclophosphamide. Using cut-off criteria previously shown to correlate with "sensitive" and "resistant" tumors for single drugs, 11% of tumors showed increased sensitivity to a combination compared with the single drugs, but 10% showed decreased sensitivity to a combination. The majority of tumors remained in the same "sensitive" or "resistant" categories obtained with the single drugs. Analysis by isobolograms demonstrated synergy, addition or antagonism with the same combination on different tumors. No significant difference between combinations and the best single drug used alone was found in 70% of assays. Overall thymidine incorporation inhibition by the combination and by the best single drug was highly correlated. It is suggested that the best single drug predicts the effectiveness of its combination regimens.
Hayward
I P
IP
University of Queensland, Department of Obstetrics and Gynecology, Royal Brisbane Hospital, Australia.
Hurst
T
T
Parsons
P G
PG
Khoo
S K
SK
D000230:Adenocarcinoma / Q000188:drug therapy*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002699:Chlorambucil / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D004354:Drug Screening Assays, Antitumor; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured
D002699:Chlorambucil; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin; D013936:Thymidine