Comparison of U-73,975 and cisplatin cytotoxicity in fresh cervical and ovarian carcinoma specimens with the ATP-chemosensitivity assay.
U-73,975 (U-73), a closely related synthetic analogue of the antitumor agent CC-1065, acts by binding tightly in the minor groove of DNA. A comparison was made between the cytotoxicity of U-73 and cisplatin (DDP) on 11 fresh cervical and 7 fresh ovarian carcinoma specimens. The ATP-chemosensitivity assay as previously described (Sevin et al. Gynecol. Oncol. 31, 191-204, 1988) was used to determine the cytotoxic effect of U-73 and DDP. IC 50s were calculated using regression analysis. The mean IC 50s for U-73 and DDP were 519 pg/ml and 2918 ng/ml, respectively, for the cervical carcinoma specimens and 324 pg/ml and 2649 ng/ml, respectively, for the ovarian carcinoma specimens. Significance comparing U-73 and DDP for cervical and ovarian tissue was demonstrated with P < 0.001. U-73 was 4000 times as cytotoxic per unit of mass as DDP on cervical carcinoma compared to over 8000 times for ovarian carcinoma. Based on these in vitro data, U-73 appears to be a very promising antitumor agent for cervical and ovarian carcinoma.
Hightower
R D
RD
Department of Obstetrics and Gynecology, University of Miami School of Medicine, Florida 33101.
Sevin
B U
BU
Perras
J P
JP
Untch
M
M
Angioli
R
R
Ramos
R
R
Averette
H
H
D000255:Adenosine Triphosphate / Q000032:analysis*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001572:Benzofurans; D002945:Cisplatin / Q000494:pharmacology*; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D053138:Cyclohexenes; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D000080890:Duocarmycins; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000188:drug therapy*; D012044:Regression Analysis; D002583:Uterine Cervical Neoplasms / Q000737:chemistry / Q000188:drug therapy*
D000970:Antineoplastic Agents; D001572:Benzofurans; D003509:Cyclohexanecarboxylic Acids; D053138:Cyclohexenes; D000080890:Duocarmycins; D007211:Indoles; C060090:adozelesin; D000255:Adenosine Triphosphate; D002945:Cisplatin