Skip to main content
Log in

Activity of 4′-0-tetrahydropyranyladriamycin hydrochloride (THP-ADM) in a human tumor cloning system

  • Preclinical
  • Published:
Investigational New Drugs Aims and scope Submit manuscript

Summary

4′-0-tetrahydropyranyladriamycin hydrochloride (THP-ADM) is a new anthracycline derivative. The antitumor activity of THP-ADM was tested on 51 human tumor samples representing ten different tumor types in in vitro colony assay method. Tested tumors were: 26 cases of ovarian cancer, 8 cases of breast cancer, 6 cases of colorectal cancer, 3 cases of endometrial cancer, 2 cases each with gastric cancer and sarcoma, and another 4 cases. An in vitro colony assay was done in soft agar as described by Hamburger & Salmon. The criteria for in vitro sensitivity was defined as a 70 percent or greater reduction in the number of colonies after a 1-h exposure to drugs. The selected concentrations of THP-ADM for assay were 0.05, 0.5, and 1.0 μg/ml. The sensitivity rates for THP-ADM in each dose were: 0.05 μg/ml (7/19, 37%), 0.5 μg/ml (10/51, 20%), and 1.0 μg/ml (12/19, 63%). In vitro sensitivity of adriamycin (0.04 μg/ml) was simultaneously tested in 49 cancer patients. Five out of 25 ovarian cancer patients (20%) showed responses to adriamycin and an overall response rate was 12% (6/49). These data indicate that THP-ADM has an antitumor activity against various cancers and it is comparable to that of adriamycin.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Umezawa H, Takahashi Y, Kinoshita M, Naganawa H, Masuda T, Ishizuka M, Tatsuta K, Takeuchi T: Tetrahydropyranyl derivatives of daunomycin and adriamycin. J Antibiot (Tokyo) 32:1082–1084, 1979

    Google Scholar 

  2. Tsuruo T, Iida H, Tsukagoshi S, Sakurai Y: 4′-0-tetrahydropyranyladriamycin as a potential new antitumor agent. Cancer Res 42:1462–1467, 1982

    Google Scholar 

  3. Dantchev D, Paintrand M, Hayat M, Bourut C, Mathé G: Low heart and skin toxicity of a tetrahydropyranyl derivative of adriamycin (THP-ADM) as observed by electron and light microscopy. J Antibiot (Tokyo) 32:1085–1086, 1979

    Google Scholar 

  4. Ogawa M, Miyamoto H, Inagaki J, Horikoshi N, Ezaki K, Inoue K, Ikeda K, Usui N, Nakada H: Phase I clinical trial of a new anthracycline: 4′-0-tetrahydropyranyl adriamycin. Jap J Clin Oncol 10(1):129–133, 1983

    Google Scholar 

  5. Hamburger AW, Salmon SE: Primary bioassay of human tumor stem cells. Science 197:461–463, 1977

    Google Scholar 

  6. Hamburger AW, Salmon SE: Primary bioassay of human myeloma stem cells. J Clin Invest 60:846–854, 1977

    Google Scholar 

  7. Carter SK: Adriamycin — a review. J Natl Cancer Inst 55:1265–1274, 1975

    Google Scholar 

  8. Alberts DS, Chen HSG: Tabular summary of pharmacokinetic parameters relevant to in vitro drug assay. In: SE Salmon (ed): Cloning of Human Tumor Stem Cells. Alan R. Liss, Inc., New York, 1980, pp 351–359

    Google Scholar 

  9. Miyamoto H, Inoue K, Arakawa M, Ogawa M: Chemosensitivity of adriamycin, mitomycin C and bleomycin with in vitro colony assay. Jap J Clin Oncol 9(11):1921–1927, 1982

    Google Scholar 

  10. Von Hoff DD, Coltman Jr CA, Forseth B: Activity of mitoxantrone in a human tumor cloning system. Cancer Res 41:1853–1855, 1981

    Google Scholar 

  11. Anderson KC, Cohen GI, Garnick MB: Phase II trial of mitoxantrone. Cancer Treat Rep 66(11):1929–1931, 1982

    Google Scholar 

  12. Ahmann FR, Meyskens FL, Moon TE, Durie BGM, Salmon SE: In vitro chemosensitivities of human tumor stem cells to the Phase II drug 4′-(9-acridinylamino)methanesulfon-m-anisidide and prospective in vivo correlations. Cancer Res 42:4495–4498, 1982

    Google Scholar 

  13. Legha SS, Keating MJ, Zander AR, McCredie KB, Bodey GP, Freireich EJ: 4′-(9-acridinylamino)methanesulfon-manisidide (AMSA): a new drug effective in the treatment of adult acute leukemia. Ann Int Med 93:17–21, 1980

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Inoue, K., Arakawa, M., Miyamoto, H. et al. Activity of 4′-0-tetrahydropyranyladriamycin hydrochloride (THP-ADM) in a human tumor cloning system. Invest New Drugs 1, 271–275 (1983). https://doi.org/10.1007/BF00177409

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00177409

Key words

Navigation