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Effect of WR-2721 on the toxicity and antitumor activity of the combination of carboplatin and 5-fluorouracil

  • Original Articles
  • WR-2721, Antitumor Activity, Toxicity, Carboplatin, Carboplatin, 5-Fluorouracil
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Summary

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 C57Bl/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 C57Bl/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.

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Authors and Affiliations

  1. Department of Oncology, Free University Hospital, PO Box 7057, 1007 MB, Amsterdam, The Netherlands

    J. A. M. van Laar, C. L. van der Wilt, M. Treskes, W. J. F. van der Vijgh & G. J. Peters

Authors
  1. J. A. M. van Laar
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  2. C. L. van der Wilt
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  3. M. Treskes
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  4. W. J. F. van der Vijgh
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  5. G. J. Peters
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Additional information

This study was supported by a grant from the Dutch Cancer Society (IKA 88-20) and by U.S. Biosciences (West Conshohocken, Pa., USA). One of the authors (G.J.P.) is a senior research fellow of the Royal Netherlands Academy of Sciences

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van Laar, J.A.M., van der Wilt, C.L., Treskes, M. et al. Effect of WR-2721 on the toxicity and antitumor activity of the combination of carboplatin and 5-fluorouracil. Cancer Chemother. Pharmacol. 31, 97–102 (1992). https://doi.org/10.1007/BF00685094

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  • DOI: https://doi.org/10.1007/BF00685094

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