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. 2011 Aug;68(2):399-403.
doi: 10.1007/s00280-010-1498-3. Epub 2010 Nov 11.

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

William R Waud  1 , Karen S Gilbert, John A Secrist 3rd
Affiliations

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

William R Waud et al. Cancer Chemother Pharmacol. 2011 Aug.

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.

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