levoleucovorin and Thymoma

Although aminopterin(AMN)-antibody drug conjugates have been demonstrated to have a greatly increased antitumor efficacy compared to the free drug, their use is limited by an increase in systemic toxicity manifested by weight loss and bone marrow suppression. Using a murine thymoma model (E3) in inbred mice, the toxicity of a sublethal dose of free AMN could be prevented by the administration of leucovorin 24 h following drug treatment, whilst maintaining the antitumour effect of the drug. The same rescue protocol completely abrogated the antitumour efficacy of AMN-antibody, although toxicity was also diminished. However, the later administration of leucovorin 48-72 h following a sublethal dose of AMN-antibody conjugates resulted in a maintenance of the anti-tumour efficacy of the immunoconjugates and a reduction in toxicity, with a mean percentage change in mouse weight not significantly different from that of the controls. These studies demonstrate that reversal of toxicity caused by AMN-antibody conjugates can be achieved by leucovorin while maintaining a powerful antitumour effect provided that the dose of leucovorin is administered 48-72 h after the conjugate.

Topics: Aminopterin; Animals; Antibodies, Monoclonal; Antigens, Ly; Immunotoxins; Leucovorin; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neoplasm Transplantation; Thymoma; Thymus Neoplasms