[Phase I and pharmacokinetic study of KRN8602, a new morpholino anthracycline].
Phase I clinical trial of a new semi-synthetic morpholino anthracycline derivative, KRN8602, was performed. Sixteen patients with advanced malignant neoplasms refractory to standard chemotherapies received 27 courses at doses ranging from 1.5 mg/m2/day to 18 mg/m2/day by bolus injection for three consecutive days. The dose limiting toxicity was leukopenia, and a maximally tolerated dose was 18 mg/m2/day (day 1-3). The recommended dose and schedule for a phase II study is determined to be 12 mg/m2/day for three consecutive days at 3-4 weeks intervals. Among non-hematologic toxicities, nausea and vomiting were severe, but stomatitis and alopecia were rarely observed. Clinical signs of cardiotoxicity were not seen.
Tabata
M
M
Dept. of Clinical Oncology, Japanese Foundation for Cancer Research, Tokyo.
Ogawa
M
M
Horikoshi
N
N
Inoue
K
K
Mukaiyama
T
T
Nagamine
D
D
Shinagawa
K
K
Fukutani
H
H
Hirano
A
A
Mizunuma
N
N
D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy*; D002360:Carubicin / Q000031:analogs & derivatives*; D004341:Drug Evaluation; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D013921:Thrombocytopenia / Q000139:chemically induced
D000903:Antibiotics, Antineoplastic; C053537:morpholinoanthracycline MX2; D002360:Carubicin