Initial clinical evaluation of N-trifluoroacetyladriamycin-14-valerate (AD-32), an adriamycin analog.

• Abstract: N-Trifluoroacetyladriamycin-14-valerate (AD-32) is superior to Adriamycin in murine L1210 and P388 leukemias and in a number of solid tumor systems, including Ridgway osteogenic sarcoma and Lewis lung carcinoma. In preclinical toxicology studies, AD-32 was less toxic than Adriamycin in both tumor- and non-tumor-being mice and in rabbits. An initial clinical trial was carried out in 23 patients who received a total of 74 courses of AD-32 over a dose range of 100--700 mg/m2 administered at 21-day intervals. Hydrocortisone given during the period of infusion prevented all clinical manifestations of acute toxicity. The AD-32 dose-limiting toxicity, leukopenia, was comparable to that of Adriamycin at a dose of 10:1, but at these equivalently myelosuppressive doses, AD-32 induced less gastrointestinal toxicity and alopecia than Adriamycin and it did not cause local tissue damage following inadvertent paravenous extravasation. Although two responses are reported, the therapeutic activity of AD-32 cannot be assessed because of an inadequate number of patients in any given tumor type. A phase II study is being initiated at a dose of 600 mg/m2 given at 21-day intervals.
• Authors: R H Blum, M B Garnick, M Israel, G P Canellos, I C Henderson, E Frei 3rd
• Journal: Cancer treatment reports (Cancer Treat Rep) Vol. 63 Issue 5 Pg. 919-23 (May 1979) ISSN: 0361-5960 [Print] UNITED STATES
• PMID: 455334 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Doxorubicin

Topics

• Doxorubicin (administration & dosage, adverse effects, analogs & derivatives, pharmacology, therapeutic use)
• Drug Evaluation
• Female
• Humans
• Male
• Neoplasms (drug therapy)