Phase I trial with 4′-deoxydoxorubicin (esorubicin)

Summary

4′-Deoxydoxorubicin is a new anthracycline derivative. Experimentally, the drug shows efficacy against doxorubicin-resistant malignancies and, as compared to the parent compound, it has reduced potential for heart damage. This Phase I trial was conducted with a single dose intermittent schedule. 4′-Deoxydoxorubicin was given by rapid i.v. administration at doses of 20, 30, 35 and 40 mg/m². A total of 25 adult patients with a variety of solid tumors received a median of two courses (1–4). Leukopenia was dose-related and dose-limiting. Occasionally severe thrombocytopenia was also encountered. Nonhematological toxic effects were mostly mild to moderate and were qualitatively similar to those commonly reported with doxorubicin. The frequency of local reactions was apparently increased but the incidence of alopecia and gastrointestinal distress was noticeably lower. There were no acute or chronic drug-induced cardiac effects. Antitumor activity was suggested in a patient with a carcinoma of the cardia. For Phase II trials, doses of 35 and 30 mg/m² every 3–4 weeks may be recommended in good-risk and poor-risk patients, respectively.