Toxicity, pharmacokinetics and metabolism of iododoxorubicin in cancer patients.
25 patients, mostly pretreated, received 55 courses of iododoxorubicin as a single intravenous bolus every 2 weeks. The starting dose was 2 mg/m2 with seven steps to reach the dose-limiting toxicity level. 3 patients treated with 90 mg/m2 had WHO grade 4 myelotoxicity; 2 of these patients had not had cytostatic chemotherapy. 3 of 7 patients treated with 75 mg/m2 had grade 3-4 myelotoxicity; 4 had grade 1-2. Non-haematological toxicities were minor. Acute cardiotoxicity and objective tumour responses were not observed. Plasma and urine levels of iododoxorubicin and five metabolites were assayed in 16 patients. Metabolism to iododoxorubicinol was rapid and plasma clearance was dose-dependent and rapid. Plasma levels and the area under the curve for iododoxorubicin increased with dose. The mean residence time was 3.9 h in patients without liver metastasis and 10.4 h in patients with liver metastasis. Renal excretion was minor. The maximally tolerated dose was 90 mg/m2.
Mross
K
K
Department of Medicine, University Clinic Eppendorf, Hamburg, F.R.G.
Mayer
U
U
Langenbuch
T
T
Hamm
K
K
Burk
K
K
Hossfeld
D
D
D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*
C053044:4'-deoxy-4'-iododoxorubicin; D004317:Doxorubicin