Abstract
The biochemical and pharmacological effects of Escherichia coli asparaginase were studied in 45 patients with leukemia and solid tumors. The drug was given in three different schedules: as a single dose, daily, or weekly. After i.v. injection, the peak activity obtained was dose related; the initial clearance of the enzyme from plasma followed first-order kinetics, and a half-life was about 14 to 22 hr. Daily administration of the enzyme caused cumulation in serum. Enzyme activity was detectable 13 to 22 days after single injections. Plasma asparagine and aspartic acid levels in leukemia were compared with levels in 20 normal individuals. Three of 10 patients with acute lymphocytic leukemia had marked aberration in their amino acid levels. Patients with acute myelocytic leukemia as a group had lowered levels of asparagine. After enzyme administration, plasma asparagine fell precipitously to nearly unmeasureable levels. Asparagine reappeared in plasma 23 to 33 days after single injections. Even 0.2 i.u./kg as a skin test dose produced a substantial fall of plasma asparagine. Asparaginase produced multiple manifestations of toxicity involving brain, liver, pancreas, kidney, fingernail, and hypersensitivity reactions. Asparagine was given as a “rescue” infusion in three patients for acute brain dysfunction with benefit. Ten of 24 patients with acute lymphocytic leukemia and 1 of 12 patients with acute myelocytic leukemia were induced to bone marrow rating 1 marrow remission, 2 after single injections. It was difficult to correlate response in vivo and a requirement of the leukemic cells for asparagine in vitro.
| Original language | English |
|---|---|
| Pages (from-to) | 2297-2305 |
| Number of pages | 9 |
| Journal | Cancer Research |
| Volume | 30 |
| Issue number | 9 |
| State | Published - Sep 1970 |
| Externally published | Yes |