title: In vitro phase II comparison of the cytotoxicity of a novel platinum analog, nedaplatin (254-S), with that of cisplatin and carboplatin against fresh, human cervical cancers.
abstract: OBJECTIVE
  To compare the in vitro cytotoxicity of nedaplatin, an investigational platinum analog, with that of cisplatin and carboplatin against fresh cervical cancers from untreated patients.
  
  
  METHODS
  Specimens were obtained prior to irradiation or radical surgery from 20 patients with locally invasive cervical carcinoma. Cytotoxicity was measured after single cell suspensions were grown in agar using colony counts and incorporation of [3H]thymidine. Nedaplatin and cisplatin were tested at 1 and 10 micrograms/ml dose levels while carboplatin was tested at 10 and 100 micrograms/ml dose levels continuously. When single hour exposures were used, drug doses were increased by 10-fold.
  
  
  RESULTS
  The median drug concentrations associated with a 50% inhibition of growth (IC50) for nedaplatin, cisplatin, and carboplatin were 0.435, 0.73, and 18.6 micrograms/ml, respectively. At 10 micrograms/ml for both cisplatin and nedaplatin and 100 micrograms/ml for carboplatin, cisplatin was the most active drug with 70% of tumors sensitive (</=50% survival relative to control plates) to cisplatin and 45 and 50% sensitive to nedaplatin and carboplatin, respectively (P = 0.015, P = 0.074). Six of 20 (30%) tumors resistant to cisplatin were also resistant to nedaplatin and carboplatin.
  
  
  CONCLUSIONS
  At doses approximating clinically achievable drug concentrations as defined by the mean plasma concentration time product, cisplatin appears more cytotoxic in vitro than either carboplatin or nedaplatin among chemotherapy-naive cervical cancers. However, nedaplatin and carboplatin are also active agents with similar activity. Since differences in drug sensitivity may be related to subtle differences in dose and schedule and the pharmacokinetics and safety profile of nedaplatin are favorable, clinical trials of nedaplatin are indicated.
authors.affiliation: Department of Obstetrics and Gynecology, Texas Tech University Health Sciences Center, Lubbock, Texas, 79430, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Monk
authors.forename: D S
authors.initials: DS
authors.lastname: Alberts
authors.forename: R A
authors.initials: RA
authors.lastname: Burger
authors.forename: P T
authors.initials: PT
authors.lastname: Fanta
authors.forename: A V
authors.initials: AV
authors.lastname: Hallum
authors.forename: K D
authors.initials: KD
authors.lastname: Hatch
authors.forename: S E
authors.initials: SE
authors.lastname: Salmon
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D016190:Carboplatin / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C053989:nedaplatin; D016190:Carboplatin; D002945:Cisplatin