title: Effect of WR-2721 on the toxicity and antitumor activity of the combination of carboplatin and 5-fluorouracil.
abstract: We evaluated the effects of WR-2721 on the toxicity and antitumor activity of the combination of 5-fluorouracil (5FU) and carboplatin (CBDCA) in BALB/c and C57B1/6 mice. On a weekly schedule, i.p. injection of 200 mg/kg WR-2721 at 5 min prior to the administration of this combination enabled us to increase the CBDCA dose from a nontoxic level of 45 mg/kg to a normally toxic dose of 60 mg/kg in non-tumor-bearing BALB/c mice while maintaining the 5FU dose at 100 mg/kg. When WR-2721 was given 30 min before this combination, the CBDCA dose could not be increased to 60 mg/kg without producing drug-related deaths. WR-2721 protected against CBDCA- and 5-FU-induced thrombocytopenia but did not prevent leukopenia or anemia in C57B1/6 mice. The antitumor activity of the combination against colon 26 tumors in BALB/c mice was increased by pretreatment with WR-2721, which facilitated elevation of the CBDCA dose to 60 mg/kg in combination with 100 mg/kg 5FU. These results reveal better therapeutic efficacy for the combination of 5FU and CBDCA following pretreatment with WR-2721.
authors.affiliation: Department of Oncology, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: J A
authors.initials: JA
authors.lastname: van Laar
authors.forename: C L
authors.initials: CL
authors.lastname: van der Wilt
authors.forename: M
authors.initials: M
authors.lastname: Treskes
authors.forename: W J
authors.initials: WJ
authors.lastname: van der Vijgh
authors.forename: G J
authors.initials: GJ
authors.lastname: Peters
mesh_terms: D004999:Amifostine / Q000494:pharmacology*; D000740:Anemia / Q000139:chemically induced; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity*; D016190:Carboplatin / Q000627:therapeutic use / Q000633:toxicity; D003110:Colonic Neoplasms / Q000188:drug therapy*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use / Q000633:toxicity; D007970:Leukopenia / Q000139:chemically induced; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D013921:Thrombocytopenia / Q000139:chemically induced; D015431:Weight Loss / Q000187:drug effects
chemical_list: D016190:Carboplatin; D004999:Amifostine; D005472:Fluorouracil