indicine-n-oxide and Leukemia--Lymphoid

Indicine N-oxide, the first pyrrolizidine alkaloid N-oxide to be studied in the treatment of cancer in humans, was administered to ten patients: four children and two adolescents with refractory acute lymphocytic leukemia and four adults with refractory acute nonlymphocytic leukemia (three acute myelocytic, one myelomonocytic). Two patients, a 4-year-old boy with acute lymphocytic leukemia and a 22-year-old man with acute myelocytic leukemia, achieved complete remission lasting 3 and 5+ months, respectively. Another 15-year-old male with acute lymphocytic leukemia had a partial remission for four months. Toxicities included bone marrow suppression, mild anorexia and nausea, and transient elevation of liver enzymes. Jaundice and liver failure, presumably induced by drug, occurred in two patients.

Topics: Adolescent; Adult; Antineoplastic Agents, Phytogenic; Child; Child, Preschool; Clinical Trials as Topic; Cyclic N-Oxides; Drug Administration Schedule; Female; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocyte Count; Male; Middle Aged; Pyrrolizidine Alkaloids

Topics: Acute Disease; Adult; Aged; Antineoplastic Agents, Phytogenic; Autopsy; Chemical and Drug Induced Liver Injury; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Middle Aged; Pancytopenia; Pyrrolizidine Alkaloids; Vascular Diseases

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.

Topics: Acute Disease; Adolescent; Adult; Aged; Antineoplastic Agents, Phytogenic; Child; Child, Preschool; Drug Administration Schedule; Drug Resistance; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Middle Aged; Pyrrolizidine Alkaloids