[Phase I study of a new antitumor antibiotic, neothramycin]

Phase I study of a new antitumor antibiotic, neothramycin which belongs to anthramycins was performed by a cooperative study group involving 15 major institutions. A total of 63 cases including 42 various solid tumors and 21 hematologic tumors refractory to standard treatments underwent the study during June 1979 to June 1981. Doses of single injection were escalated from an initial dose of 2 mg/m2 estimated by one twentieth of LD10 in mice up to 60 mg/m2. The most frequent and severest toxicity was nausea and vomiting seen in about the half of patients being administered dosages ranged from 24 mg/m2 to 40 mg/m2, and 3 out of 4 patients received dosages exceeding 50 mg/m2 required clinical managements; moreover, 1 out of 2 patients administered 60 mg/m2 was ranked as grade 4 of the criterion of toxicities in WHO handbook. Other clinical toxicities such as skin rash, hepatotoxicity or nephrotoxicity observed in the minority of the patients were reversible. Furthermore, hematologic toxicity was extremely mild and appeared not to be dose dependent. One patient with chronic myelogeneous leukemia had a hematological improvement and the other with esophageal cancer had a partial response. The result indicates that a dose limiting factor of neothramycin is nausea and vomiting, and a maximum tolerated dose of a single injection is 60 mg/m2. A dose schedule of 30-40 mg/m2 appears to be an optimal dose for Phase II study.