Lithium-Carbonate as a Protectant Against Chemotherapy-Induced Myelosuppression

172 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1985.Lithium carbonate has been used as an adjunct to cancer chemotherapy to lessen the dose-limiting myelosuppressive effects of several anti-cancer drugs. Its mechanism is unknown, but several possible sites of action have been considered. Lithium causes a neutrophilia and may protect the bone marrow against the toxic effects of myelosuppressive drugs.The present study first investigated the pharmacokinetics of lithium in normal dogs in a crossover study of eight dogs. An iterative least squares computation was used to determine a dosage schedule based on the plasma lithium concentrations obtained. A dose of 12.24 mg/kg q 12 h was calculated to maintain serum lithium concentrations of 0.8 to 1.5 mEq/L in normal dogs. This dose was within the range previously used in other canine experiments but failed to maintain serum lithium concentrations between 0.8 and 1.5 mEq/L in this study.In a second set of experiments, twenty-four dogs were used to evaluate the efficacy of lithium carbonate in preventing chemotherapy-induced myelosuppression. Vinblastine sulfate and nitrogen mustard were used as myelosuppressive agents in separate trials. In each trial, half the dogs received lithium carbonate for six days prior to treatment with the myelosuppressive drug. Changes in the hemogram were followed daily throughout the course of the study. Numbers of bone marrow progenitor cells and the quantity of colony-stimulating activity were measured by assaying the numbers of progenitor cell colonies grown in a semi-solid agar culture system. Statistical evaluation indicated: (1) Lithium carbonate did cause a transient neutrophilia. (2) But lithium carbonate was not effective in preventing myelosuppression. There also appeared to be a lethal interaction between lithium and nitrogen mustard as administered in this study. Some of the results conflict with those of other experiments in dogs and clinical trials in people. The conflicts indicate a need for further work to clarify both the mechanism of action of lithium and its role in the clinic.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD