Lack of in vivo cross-resistance with 4′-thio-ara-C against drug-resistant murine P388 and L1210 leukemias

Academic Article

Abstract

  • Purpose: 4′-Thio-β-D-arabinofuranosylcytosine (4′-thio-ara-C), which has shown a broad spectrum of antitumor activity against human tumor systems in mice and is undergoing clinical trials, was evaluated for cross-resistance to seven clinical agents in order to identify potentially useful guides for patient selection for further clinical trials of 4′-thio-ara-C and possible noncross-resistant drug combinations with 4′-thio-ara-C. Methods: A drug resistance profile for 4′-thio-ara-C, which was administered intraperitoneally daily for nine consecutive days, was obtained using seven drug-resistant P388 and L1210 leukemias that were implanted intraperitoneally in mice. Results: Multidrug-resistant P388 leukemias (leukemias resistant to doxorubicin, etoposide, or paclitaxel) exhibited no cross-resistance to 4′-thio-ara-C. Leukemias resistant to camptothecin, cisplatin, and 5-fluorouracil were also not cross-resistant to 4′-thio-ara-C. Only the leukemia resistant to 1-β-D- arabinofuranosylcytosine was cross-resistant to 4′-thio-ara-C. Conclusions: The data suggest that (1) it may be important to exclude or to monitor with extra care patients who have previously been treated with 1-β-D-arabinofuranosylcytosine and (2) the lack of cross-resistance seen with 4′-thio-ara-C may contribute to therapeutic synergism when 4′-thio-ara-C is combined with other agents. © 2010 Springer-Verlag.
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    Digital Object Identifier (doi)

    Author List

  • Waud WR; Gilbert KS; Secrist JA
  • Start Page

  • 399
  • End Page

  • 403
  • Volume

  • 68
  • Issue

  • 2