title: In vitro and in vivo antineoplastic activity of a new platinum antineoplastic agent, (R)-(-)-1,1-cyclobutanedicarboxylate (2-aminomethylpyrrolidine)-platinum (II) (DWA2114R) on freshly separated human tumor cells and human tumor xenografts transplanted in nude mice--a comparison with cis-diammine-dichloroplatinum (CDDP).
abstract: The in vitro antimetabolic effect of a newly synthesized platinum antineoplastic agent, DWA2114R, on 72 fresh human tumors was compared with that of cis-platinum (CDDP). DWA2114R is reported to have a lower nephrotoxicity than CDDP, but is as strong an inhibitor of DNA synthesis as CDDP. In vitro IC50 was assessed in 10 tumors; the IC50 of DWA2114R ranged between 9.2 and 107 microM (mean +/- S.D., 45.9 +/- 36.6) and that of CDDP ranged between 0.9 and 40 microM (18.3 +/- 15.1). DWA2114R had an antitumor spectrum similar to that of CDDP. Primary esophageal and pancreatic cancers were sensitive to DWA2114R, and cells separated from malignant effusion or metastatic lymph nodes were more sensitive than those from primary lesions. Nude mice were transplanted with 3 kinds of human tumor xenografts (esophageal, pancreatic and bile duct cancer lines), and were then treated with CDDP or DWA2114R at 4 times the clinical doses. CDDP significantly inhibited the growth of all the 3 lines, and DWA2114R inhibited the growth of 2 of the lines. The effect of DWA2114R on body weight was smaller than that of CDDP. These results suggest that DWA2114R may be less potent than CDDP but may be useful as a new platinum antineoplastic agent with lower grade of side effects than CDDP.
authors.affiliation: First Department of Surgery, Kyoto University Faculty of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Nio
authors.forename: S
authors.initials: S
authors.lastname: Imai
authors.forename: T
authors.initials: T
authors.lastname: Shiraishi
authors.forename: M
authors.initials: M
authors.lastname: Tsubono
authors.forename: H
authors.initials: H
authors.lastname: Morimoto
authors.forename: C C
authors.initials: CC
authors.lastname: Tseng
authors.forename: T
authors.initials: T
authors.lastname: Tobe
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001650:Bile Duct Neoplasms / Q000188:drug therapy*; D016190:Carboplatin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002277:Carcinoma / Q000188:drug therapy*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D002460:Cell Line; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use; D004261:DNA Replication / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004938:Esophageal Neoplasms / Q000188:drug therapy*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D012334:RNA, Neoplasm / Q000096:biosynthesis; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; C058816:DWA 2114; D016190:Carboplatin; D002945:Cisplatin