Preclinical Rationale and Phase I Clinical Trial of the Adriamycin Analog, AD 32

  • R. H. Blum
  • M. B. Garnick
  • M. Israel
  • G. P. Panellos
  • I. C. Henderson
  • E. FreiIII
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 76)


The preclinical and clinical data for the adriamycin analog (AD 32) will be reviewed and compared to adriamycin. Emphasis will be placed on demonstrated biologic differences that may make AD 32 the better compound for clinical use.


High Performance Liquid Chromatography Cardiac Toxicity Endomyocardial Biopsy Aldoketo Reductase Preclinical Rationale 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Billingham ME, Mason JW, Bristow MR, Daniels JR (1978) Anthracycline cardiomyopathy monitored by morphologic changes. Cancer Treat Rep 62: 865–872PubMedGoogle Scholar
  2. 2.
    Blum RH, Garnick MB, Israel M, Canellos GP, Henderson IC, Frei III E (to be published) Initial clinical evaluation of N-trifluoracetyladriamycin-14-valerate (AD 32), and adriamycin analog. Cancer Treat Rep 63Google Scholar
  3. 3.
    Bristow MR, Mason JW, Billingham ME, Daniels JR (1978) Duxorubicin cardiomyopathy: Evaluation by phonocardiography, endomyocardial biopsy and cardiac catheterization. Ann Intern Med 88:168–175PubMedGoogle Scholar
  4. 4.
    Facchinetti T, Mantovani A, Cantoni L, Cantoni R, Salmona M (1978) Intercalation with DNA is a prerequisite for daunomycin, adriamycin and its congeners in inhibiting DNAase I. Chem Biol Interact 20:97–102PubMedCrossRefGoogle Scholar
  5. 5.
    Frei III E, Luce JK, Middleman E (1972) Clinical trials of adriamycin. In: Carter SK, DiMarco A, Ghione M, Krakoff IH, Mathe G (eds) International symposium of adriamycin. Springer, Berlin Heidelberg New York, pp 153–160CrossRefGoogle Scholar
  6. 6.
    Garnick MB, Israel M, Pegg WJ, Blum RH, Smith E, Frei III E (1979) Hepatobiliary pharmacokinetics of AD 32 in man. Proc Am Assoc Cancer Res 20:206Google Scholar
  7. 7.
    Henderson IC, Billingham M, Israel M, Krishan A, Frei III E (1978) Comparative cardiotoxicity studies with adriamycin (ADR) and AD 32 in rabbits. Proc Am Assoc Cancer Res 19:158Google Scholar
  8. 8.
    Israel M, Garnick MB, Pegg WJ, Blum RH, Frei III E (1978) Preliminary pharmacology of AD 32 in man. Proc Am Assoc Cancer Res 19:160Google Scholar
  9. 9.
    Israel M, Modest EJ, Frei III E (1975) N-trifluoroacetyladriamycin-14-valerate, an analog with greater experimental antitumor activity and less toxicity than adriamycin. Cancer Res 35:1365–1368PubMedGoogle Scholar
  10. 10.
    Israel M, Pegg WJ, Wilkinson PM, Garnick MB (1979) HPLC applications in the analysis of adriamycin and analogs in biological fluids. In: Hawk GL (ed) Biological-biomedical applications of liquid chromatography. Dekker, New York, pp 413–428Google Scholar
  11. 11.
    Israel M, Pegg WJ, Wilkinson PM (1978) Urinary anthracycline metabolites from mice treated with adriamycin and N-trifluoroacetyladriamycin-14-valerate. J Pharmacol Exp Ther 204:696–701PubMedGoogle Scholar
  12. 12.
    Israel M, Wilkinson PM, Osteen RT (1978) Comparative pharmacology of adriamycin and N-trifluoroacetyladriamycin-14-valerate in the monkey. Int Cancer Congr (Abstr) 1:279Google Scholar
  13. 13.
    Israel M, Wilkinson PM, Pegg WJ, Frei III E (1978) Hepatobiliary metabolism and excretion of adriamycin and N-trifluoroacetyladriamycin-14-valerate in the rat. Cancer Res 38:365–370PubMedGoogle Scholar
  14. 14.
    Krishan A, Dutt K, Israel M Personal communicationGoogle Scholar
  15. 15.
    Krishan A, Ganapathi RN, Israel M (1978) Effect of adriamycin and analogs on the nuclear fluorescence of propidium iodide-stained cells. Cancer Res 38:3656–3662PubMedGoogle Scholar
  16. 16.
    Krishan A, Israel M, Modest EJ, Frei III E (1976) Differences in cellular uptake and cytofluorescence of adriamycin and N-trifluoroacetyl-adriamycin-14-valerate. Cancer Res 36:2114–2116Google Scholar
  17. 17.
    Lazarus H, Yuan G, Tan E, Israel M (1978) Comparative inhibitory effects of adriamycin, AD 32, and related compounds on in vitro cell growth and macromolecular synthesis. Proc Am Assoc Cancer Res 19:159Google Scholar
  18. 18.
    Meriwether WD, Bachur NR (1972) Inhibition of DNA and RNA metabolism by daunorubicin and adriamycin in L-1210 mouse leukemia. Cancer Res 32:1137–1142PubMedGoogle Scholar
  19. 19.
    Parker LM, Hirst M, Israel M (1978) N-trifluoroaeetyladriamycin-14-valerate: Additonal mouse antitumor and toxicity studies. Cancer Treat Rep 62:119–127PubMedGoogle Scholar
  20. 20.
    Sengupta SK, Seshadri R, Modest EJ, Israel M (1976) Comparative DNA-binding studies with adriamycin (ADR), N-trifluoroacetyladriamycin-14-valerate (AD 32) and related compounds. Proc Am Assoc Cancer Res 17:109Google Scholar
  21. 21.
    Vecchi A, Cairo M, Mantovani A, Sironi M, Spreafico F (1978) Comparative antineoplastic activity of adriamycin and N-trifluoroacetyladriamycin-14-valerate. Cancer Treat Rep 62:111–117PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1981

Authors and Affiliations

  • R. H. Blum
    • 1
  • M. B. Garnick
    • 1
  • M. Israel
    • 1
  • G. P. Panellos
    • 1
  • I. C. Henderson
    • 1
  • E. FreiIII
    • 1
  1. 1.Division of Medical Oncology and Pharmacology, Sidney Farber Cancer InstituteHavard Medical SchoolBostonUSA

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