Characteristics of the combination paclitaxel plus doxorubicin in breast cancer cell lines analyzed with the ATP-cell viability assay.
Preliminary clinical data show promising activity regarding the combination of paclitaxel (Taxol) (TAX) and doxorubicin (Adriamycin) (ADR) in the treatment of breast cancer. This combination needs both further preclinical and clinical investigations to better understand the drug interaction, and to optimize the dose and schedule of these drugs. This study was done to evaluate the combination effect of TAX and ADR in three human breast cancer cell lines. The ATP-Cell-Viability Assay was used to evaluate the chemosensitivity profiles and to obtain dose response curves. For quantitation of synergism and antagonism the median-effect principle was applied and the corresponding combination index values were calculated. Drug synergism/antagonism was shown to be dose-related; synergism was enhanced at higher fractions affected. From this preclinical data, we have concluded that TAX-ADR is highly effective and partly synergistic in vitro. In spite of severe initial toxicities in early clinical trials in metastatic breast cancer patients, further clinical studies appear to be justified in order to define a tolerable dosage.
Koechli
O R
OR
Department of Obstetrics & Gynecology, University of Miami School of Medicine, Florida 33136.
Sevin
B U
BU
Perras
J P
JP
Chou
T C
TC
Angioli
R
R
Steren
A
A
Untch
M
M
Averette
H E
HE
D000255:Adenosine Triphosphate / Q000032:analysis*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004317:Doxorubicin; D000255:Adenosine Triphosphate; D017239:Paclitaxel