Protection by WR-2721 of the toxicity induced by the combination of cisplatin and 5-fluorouracil

G. J. Peters, C. L. Van Der Wilt, F. Gyergyay, J. A M Van Laar, M. Treskes, W. J F Van Der Vijgh, H. M. Pinedo

Research output: Contribution to journalArticlepeer-review

Abstract

We evaluated the effects of WR-2721 and its metabolite WR-1065 on in vitro growth inhibition by 5-fluorouracil (5FU) and cisplatin (CDDP) and the effect of WR-2721 on in vivo toxicity and antitumor effect of 5FU and CDDP. In cell culture both WR-2721 and WR-1065 were not able to reverse growth inhibition caused by either 5FU or CDDP. Administration of WR-2721 i.p. at 525 mg/kg to mice resulted in a severe temperature drop to 27°C; at 200 mg/kg hypothermia was less severe. WR-2721 failed to prevent 5FU toxicity, but the maximum tolerated dose of CDDP in the combination with 5FU (at 100 mg/kg) could be increased from 3 to 7 mg/kg. CDDP at 7 mg/kg enhanced leukopenia caused by 5FU at 100 mg/kg to 20% and thrombocytopenia to 40%; WR-2721 reduced leukopenia and prevented thrombocytopenia induced by the combination. Combination of CDDP, 5FU, and WR-2721 resulted in an enhanced antitumor activity against the murine colon tumor Colon 26 compared to 5FU alone and to 5FU combined with CDDP at their maximum tolerated dose.

Original languageEnglish (US)
Pages (from-to)785-789
Number of pages5
JournalInternational Journal of Radiation Oncology, Biology, Physics
Volume22
Issue number4
DOIs
StatePublished - 1992
Externally publishedYes

Keywords

  • 5-fluorouracil
  • Cisplatinum
  • WR-2721 (ethiofos)

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

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