Phase I trial of indicine-N-oxide in children with leukemia and solid tumors: a Pediatric Oncology Group study.
A phase I trial of indicine-N-oxide was carried out in 12 children with solid tumors and in 16 with leukemia. Doses of 5, 6, and 7.5 g/m2 were given parenterally as a 15-min infusion every 3 weeks. The maximum tolerated dose in patients with solid tumors was 7.5 g/m2 and the dose-limiting toxicity was myelosuppression. In leukemia, the maximum tolerated dose was 6.0 g/m2 and hepatotoxicity was dose-limiting. Half of the children with leukemia showed elevations in transaminase levels and one child died of massive hepatic necrosis. This hepatotoxicity limits the use of indicine-N-oxide in children with leukemia. Antineoplastic activity was limited to a transient reduction in the numbers of circulating leukemic cells.
McGill University, Montreal, Canada.
V M
VM
Whitehead
M L
ML
Bernstein
R
R
Vega
T
T
Vats
P
P
Dyment
T J
TJ
Vietti
J
J
Krischer
D000293:Adolescent; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D006801:Humans; D007262:Infusions, Intravenous; D007938:Leukemia / Q000188:drug therapy*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009369:Neoplasms / Q000188:drug therapy*; D011763:Pyrrolizidine Alkaloids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013921:Thrombocytopenia / Q000139:chemically induced
D000972:Antineoplastic Agents, Phytogenic; D011763:Pyrrolizidine Alkaloids; C013095:indicine-N-oxide