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Positive therapeutic interaction between thiopurines and alkylating drugs in human glioma xenografts

Cancer Chemotherapy and Pharmacology volume 27, pages 278–284 (1991)Cite this article

Summary

We used human anaplastic glioma xenografts to evaluate the therapeutic efficacy of combinations of alkylating drugs, either 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), 1-(2-chloroethyl)-3-(2,5-dioxo-3-piperidyl)-1-nitrosourea (PCNU), or procarbazine, and thiopurines, either 6-mercaptopurine (6MP) or 6-thioguanine (6TG). Using growth delay as the endpoint in subcutaneous (s.c.) tumors and increased life span as the endpoint in intracranial (i.c.) tumors, we found that combinations of chloroethylnitrosoureas (CENUs) and thiopurines were significantly more active than either type of agent alone. In contrast, combinations of procarbazine and thiopurines were not significantly more active than procarbazine alone. The therapeutic potentiation of the CENU was greater when the latter was given on the 4th day of the thiopurine treatment cycle than when it was given on the 1st day. Characterization of the interaction between CENUs and thiopurines also revealed a supraadditive therapeutic response at higher BCNU doses in combination with 6TG. Interaction between the nitrosoureas and the thiopurines probably occurs in the guanine base of tumor DNA and has important therapeutic implications.

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Affiliations

  1. Division of Neurology, Duke University Medical Center, P. O. Box 3963, 27 710, Durham, NC

    Andrew M. Wang, Gertrude B. Elion, Henry S. Friedman, Darell D. Bigner & S. Clifford Schold Jr.

  2. Brain Tumor Research Center, Department of Neurosurgery, University of California School of Medicine, 94143, San Francisco, CA, USA

    William J. Bodell

Authors
  1. Andrew M. Wang
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  2. Gertrude B. Elion
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  3. Henry S. Friedman
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  4. William J. Bodell
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  5. Darell D. Bigner
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  6. S. Clifford Schold Jr.
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Additional information

This work was supported in part by the NCI (CA 44 640), by the Preuss Foundation, and by a grant from Bristol-Myers (100-R18). One of the authors (S. C. S.) is the recipient of a Jacob Javits Investigator Award from NINCDS (NS 20 581)

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Wang, A.M., Elion, G.B., Friedman, H.S. et al. Positive therapeutic interaction between thiopurines and alkylating drugs in human glioma xenografts. Cancer Chemother. Pharmacol. 27, 278–284 (1991). https://doi.org/10.1007/BF00685112

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  • DOI: https://doi.org/10.1007/BF00685112

Keywords

  • Human Glioma
  • BCNU
  • Growth Delay
  • Thiopurines
  • Procarbazine