International Journal of Cell Cloning, Vol 10, 182-189, Copyright © 1992 by AlphaMed Press
Combination chemotherapy tested in a short-term thymidine incorporation assay in primary cultures of ovarian adenocarcinomas
IP Hayward, T Hurst, PG Parsons and SK Khoo
University of Queensland, Department of Obstetrics and Gynecology, Royal Brisbane Hospital, Australia.
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.
