Hepatocellular toxicity during the treatment of refractory acute leukemia with indicine N-oxide.
Indicine N-oxide is the first member of the large class of compounds comprised of pyrrolizidine alkaloids and their N-oxides to be studied in the treatment of cancer in humans. Twenty-two patients with refractory acute leukemia received indicine N-oxide daily for 5 consecutive days in a dose-seeking study. Of eight patients with refractory acute lymphocytic leukemia, one had a complete remission, and one had a partial remission. Of 11 patients with refractory acute nonlymphocytic leukemia, 2 patients had complete remissions. Of three patients with blast crisis of chronic granulocytic leukemia, one patient had a partial remission. Five patients had severe hepatic toxicity, probably due to veno-occlusive disease induced by the drug. Whether hepatotoxicity and antileukemic activity are a result of the same mechanism of action of indicine N-oxide is not known.
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D007945:Leukemia, Lymphoid / Q000188:drug therapy; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D011763:Pyrrolizidine Alkaloids / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use
D000972:Antineoplastic Agents, Phytogenic; D011763:Pyrrolizidine Alkaloids; C013095:indicine-N-oxide