In vitro study of the interaction of doxorubicin, thiotepa, and mitomycin-C, agents used for intravesical chemotherapy of superficial bladder cancer.
Several cytotoxic agents have been identified as effective in the treatment of superficial transitional cell carcinoma of the bladder, including doxorubicin, thiotepa and mitomycin-C. An in vitro study was conducted to assess the interactions of these three drugs against a well differentiated human bladder tumor cell line, RT-4, to identify and evaluate synergistic combinations among these agents. Cytotoxicity was evaluated by a colorimetric assay based on the capacity of viable cells to metabolize a tetrazolium dye, MTT, to produce a colored formazan product. The analyses of drug interactions were done by the isobolographic method (construction of isoeffect plots). The combination of doxorubicin and thiotepa was found to be the most synergistic, followed by the combination of doxorubicin and mitomycin-C. The combination of mitomycin C and thiotepa demonstrated an unpredictable effect. These findings suggest the combination of doxorubicin and thiotepa has potential advantage for chemotherapy of superficial bladder tumors.
Seraphim
L A
LA
Department of Urologic Oncology, Roswell Park Cancer Institute, Buffalo, New York 14263.
Perrapato
S D
SD
Slocum
H K
HK
Rustum
Y M
YM
Huben
R P
RP
D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy*; D003124:Colorimetry; D004317:Doxorubicin / Q000627:therapeutic use; D004347:Drug Interactions; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D016685:Mitomycin; D008937:Mitomycins / Q000627:therapeutic use; D013852:Thiotepa / Q000627:therapeutic use; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; D008937:Mitomycins; D016685:Mitomycin; D004317:Doxorubicin; D013852:Thiotepa