KRN 8602 is a new
antineoplastic drug with the chemical structure, 3'-deamino-3'-morpholino-13-deoxo-10-hydroxycarminomycin hydrochloride. This
drug was developed in an attempt to improve the clinical efficacy of currently used
anthracyclines. In preclinical studies,
KRN 8602 has been shown to produce less
cardiotoxicity and
alopecia, yet has comparable antitumor effects to
adriamycin. In addition,
KRN 8602 has shown antitumor effects on
adriamycin-resistant
tumors. A phase I clinical study was undertaken to determine the toxicity of
KRN 8602 given as a single i.v. dose. Toxicity evaluation included CBC with differentials, platelet counts, SMA chemistry profile, EKG, urinalysis, plain chest X-ray and physical examination. Myelosuppression was the major side effect noted with
leukopenia, and especially
neutropenia, being dose-limiting. The degree of WBC suppression was dose-related and MTD appears to be 30 mg/m2.
Nausea and
vomiting were observed in cases who had received more than 10 mg/m2. No patient had
alopecia. No obvious
cardiotoxicity in this study. Maximum total cumulative dose of
KRN 8602 was 450 mg/m2. Further observation is necessary to confirm this point. In this study of 10 cases, one
breast carcinoma with bilateral lung
metastasis revealed definite regression of
metastasis for more than 18 months with this agent alone. This patient had previous chemo- and
hormone therapy, containing
adriamycin. The above preliminary phase I clinical study suggests strongly the usefulness of
KRN 8602, and further investigations are indicated.