title: Dose escalation study of tezacitabine in combination with cisplatin in patients with advanced cancer.
abstract: BACKGROUND
  The authors performed a dose escalation study of cisplatin and the novel deoxycytidine analog, tezacitabine, to determine the maximum tolerated dose of the combination.
  
  
  METHODS
  Twenty-three patients with advanced cancer and good performance status were accrued to 3 dose levels of tezacitabine (150-270 mg/m(2)) and cisplatin (50 mg/m(2)). Using a 28-day treatment cycle, both drugs were administered on Days 1 and 15.
  
  
  RESULTS
  Hematologic toxicity was the most frequently observed side effect and was dose limiting. Grade 3 or 4 neutropenia and thrombocytopenia complicated 75% and 31% of all cycles, respectively. Nonhematologic toxicities were mild. Among 18 evaluable patients, 2 with upper gastrointestinal tract tumors achieved partial responses and 4 had stable disease.
  
  
  CONCLUSIONS
  Based on dose-limiting neutropenia and thrombocytopenia at the highest dose level, the recommended Phase II doses are 200 mg/m(2) of tezacitabine and 50 mg/m(2) of cisplatin.
authors.affiliation: Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ktflaherty@aol.com
authors.forename: Keith T
authors.initials: KT
authors.lastname: Flaherty
authors.forename: James P
authors.initials: JP
authors.lastname: Stevenson
authors.forename: Maryann
authors.initials: M
authors.lastname: Gallagher
authors.forename: Bruce
authors.initials: B
authors.lastname: Giantonio
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Algazy
authors.forename: Weijing
authors.initials: W
authors.lastname: Sun
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Haller
authors.forename: Peter J
authors.initials: PJ
authors.lastname: O'Dwyer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D003841:Deoxycytidine; D002945:Cisplatin; C086432:tezacitabine