Comparison of U-73,975 and cisplatin cytotoxicity in fresh cervical and ovarian carcinoma specimens with the ATP-chemosensitivity assay

Gynecol Oncol. 1992 Nov;47(2):186-90. doi: 10.1016/0090-8258(92)90104-q.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / analysis*
  • Antineoplastic Agents / pharmacology*
  • Benzofurans
  • Cisplatin / pharmacology*
  • Cyclohexanecarboxylic Acids / pharmacology*
  • Cyclohexenes
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor / methods
  • Duocarmycins
  • Female
  • Humans
  • In Vitro Techniques
  • Indoles*
  • Ovarian Neoplasms / chemistry
  • Ovarian Neoplasms / drug therapy*
  • Regression Analysis
  • Uterine Cervical Neoplasms / chemistry
  • Uterine Cervical Neoplasms / drug therapy*

Substances

  • Antineoplastic Agents
  • Benzofurans
  • Cyclohexanecarboxylic Acids
  • Cyclohexenes
  • Duocarmycins
  • Indoles
  • adozelesin
  • Adenosine Triphosphate
  • Cisplatin