Skip to main content
Log in

Clinical evaluation of 4′-epi-doxorubicin in advanced solid tumors

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

Summary

A Phase II clinical evaluation of 4′-epi-doxorubicin has been carried out in 100 patients with various types of solid tumors. Hematopoietic toxicity was dose-limiting but reversible and of mild to moderate degree. Other acute toxic manifestations such as vomiting and alopecia were qualitatively similar to those usually reported for doxorubicin, but lower in frequency and less severe. A number of responding patients received cumulative doses of 4′-epi-doxorubicin in excess of 500 mg/m2. One patient manifested reversible clinical congestive heart failure at cumulative dose of 1,080 mg/m2. Therapeutic activity has been observed in breast carcinoma, in rectal carcinoma and in melanoma. In chemoresistant tumors as rectal cancer and melanoma 4′-epi-doxorubicin deserves further study.

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. Young RC, Ozols RE, Myers CE: The anthracyclines antineoplastic drugs. N Engl J Med 305:139–153, 1981

    Google Scholar 

  2. Arcamone F, Penco S, Vigevani A, Redaelli S, Franchi S, Di Marco A, Casazza AM, Dasdia T, Formelli F, Necco A, Soranzo C: Synthesis and antitumor properties of new glycosides of daunomycinone and adriamycinone. J Med Chem 18:703–707, 1975

    Google Scholar 

  3. Casazza AM, Di Marco A, Bertazzoli C, Formelli F, Giuliani F, Pratesi G: Antitumor activity, toxicity and pharmacological properties of 4′-epiadriamycin. Current Chemotherapy. Proceedings of the 10th International Congress of Chemotherapy 2, 1978, pp 1257–1260

  4. Casazza AM, Di Marco A, Bonadonna G, Bonfante V, Bertazzoli C, Bellini O, Pratesi G, Sala L, Ballernini L: Effects of modifications in position 4 of the chromophore or in position 4′ of the aminosugar, on the antitumor activity and toxicity of daunorubicin and doxorubicin. In: Crooke ST, Reich SD (eds) Anthracyclines: Current Status and New Developments. Academic, Press, 1980, 23, pp 403–429

  5. Bonfante V, Bonadonna G, Villani F, Di Fronzo G, Martini A, Casazza AM: Preliminary phase I study of 4′-epiadriamycin. Cancer Treat Rep 63:915–918, 1979

    Google Scholar 

  6. Schauer PK, Wittes RE, Gralla RJ, Casper ES, Young CW; A phase I trial of 4′-epi-adriamycin. Cancer Clin Trials 4:433–437, 1981

    Google Scholar 

  7. Bonfante V, Villani F, Bonadonna G: Toxic and therapeutic activity of 4′-epi-doxorubicin. Tumori 68:105–111, 1982

    Google Scholar 

  8. Blum RH, Carter SK: Adriamycin, a new anticancer drug with significant clinical activity. Ann Intern Med 80:249–259, 1974

    Google Scholar 

  9. Bonadonna G, Beretta G, Tancini G, Brambilla C, Bajetta E, De Palo GM, De Lena M, Fossati Bellani F, Gasparini M, Valagussa P, Veronesi U: Adriamycin (NSC-123127) studies at the Istituto Nazionale Tumori, Milan. Cancer Chemother Rep (part 3) 6:231–245, 1975

    Google Scholar 

  10. Broggini M, Colombo T, Martini A, Donelli MG: Studies on the comparative distribution and biliary excretion of doxorubicin and 4′-epi-doxorubicin in mice and rats. Cancer Treat Rep 63:897–904, 1980

    Google Scholar 

  11. Martini A, Isetta AM, Moro E, Natale N, Piazza E: Studio farmacocinetico nell'uomo sulla 4′-epi-doxorubicina in confronto a doxorubicina. Tumori 6 (2), Suppl A, no 40, 1980 (Abstract)

  12. Camaggi CM, Strocchi E, Tamassia V, Martoni A, Giovannini M, Infelice C, Canova N, Marraro D, Martini A, Pannuti F: Pharmacokinetics studies of 4′-epi-doxorubicin in cancer patients with normal and impaired renal function and with hepatic metastasis. Cancer Treat Rep 66:1819–1824, 1982

    Google Scholar 

  13. Weenen H, Lankelma J, Penders PGM, McWie JG, Ten Bokkel Huinink WW, de Planque MM, Pinedo HM: Pharmacokinetics of 4′-epi-doxorubicin in man. Invest N Drugs 1:59–64, 1983

    Google Scholar 

  14. Von Hoff DD, Layard MW, Basa P, Davis HL, Von Hoff AL, Rozencweig M, Muggia F: Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med 91:710–717, 1979

    Google Scholar 

  15. O'Bryan RM, Baker LH, Gottlieb JE, Rivkin SE, Balcerzak SP, Grumet GN, Salmon SE, Moon TE, Hoogstraten B: Dose response evaluation of adriamycin in human neoplasia. Cancer 39:1940–1948, 1977

    Google Scholar 

  16. Young CW, Wittes RE, Jain K, Casper ES: Clinical evaluation of 4′-epi-doxorubicin. 13th International Congress of Chemotherapy, Vienna (Austria), August 28th–September 2nd, 1983

  17. Wittes RE, Jain K, Kaufman R, Currie V, Hakes T, Bosl G, Benedetto P, Young C: A randomized comparison of 4′-epidoxorubicin (4′-ED) and doxorubicin (DOX) in advanced breast cancer. Proc Am Soc Clin Oncol 2:109, 1983 (Abstract)

    Google Scholar 

  18. Fossa SD, Wik B, Bae E, Lien HN: Phase II study of 4′-epidoxorubicin in metastatic renal cancer. Cancer Treat Rep 66:1219–1221, 1982

    Google Scholar 

  19. Kolaric K, Potrebica V, Cervek Y: Phase II clinical trial of 4′-epi-doxorubicin in metastatic solid tumors. J Cancer Res Clin Oncol 1983, (in press)

  20. Falkson G, Falkson HC, Vorobiof DA, Pretoriuss HL, Falkson CB: A phase Ii study of 4′-epi-doxorubicin in colorectal cancer. 13th International Congress of Chemotheapy, Vienna (Austria), August 28th–September 2nd, 1983

  21. Robustelli Della Cuna G, Pavesi L, Cuzzoni Q, Ganzina F, Tramarin R: A phase II study of 4′-epi-adriamycin in advanced solid tumors. Curr Chemother Immunother 2:1462–1464, 1982

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cuna, G.R.D., Pavesi, L., Preti, P. et al. Clinical evaluation of 4′-epi-doxorubicin in advanced solid tumors. Invest New Drugs 1, 349–353 (1983). https://doi.org/10.1007/BF00177421

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00177421

Key words

Navigation