AMSA toxicity in patients with abnormal liver function

4′-(9-Acridinylamino) methanesulfon-m-anisidide AMSA) is a new anti-tumor drug effective in the treatment of acute leukemia and some solid tumors. Phase I and II studies showed myelosuppression to be its major toxicity. Preliminary pharmacological studies with AMSA revealed prolongation of half-life and delayed clearance in patients with compromised liver function. In this study, we have correlated pretreatment liver function abnormalities with myelosuppressive toxicity of AMSA in patients with leukemia and a variety of solid tumors. In patients with solid tumors and elevated serum bilirubin levels, the degree of myelosuppression was unpredictable. Since some patients experienced excessive toxicity it is advisable to begin therapy with a 25-30% reduction in the starting dose of AMSA for patients with elevated bilirubin values. In leukemia patients with a serum bilirubin level up to 3 mg/dl dose reduction is not indicated, but longer duration of hypoplasia may occur. It may, however, be advisable to start at a 25% lower dose, especially if the bilirubin level is greater than 3 mg/dl. Additional pharmacokinetic studies are necessary to clarify the relationship between liver dysfunction, plasma clearance of AMSA and the degree of myelosuppression.