PHARMACODYNAMICS AND LONG-TERM TOXICITY OF ETOPOSIDE

Etoposide has been used in the treatment of a wide variety of neoplasms, including small-cell lung cancer, Kaposi's sarcoma, testicular cancer, acute leukemia, and lymphoma. Its current therapeutic use is limited by myelosuppression, particularly neutropenia. Pharmacodynamic studies of etoposide show that this toxicity can be modeled using a modified Hill equation and that the dose intensity of etoposide can be successfully increased by adaptive control using this model. Significant influences on the degree of myelosuppression include the pretreatment leukocyte count, the performance status, the extent of prior erythrocyte transfusions, and the serum albumin level. In the past 7 years, interest has developed in a distinct subset of acute nonlymphocytic leukemia that is associated with prior exposure to etoposide. This syndrome has been described in several studies and is characterized by the lack of a preleukemic phase, M4 or M5 morphology, and distinct translocations involving the chromosome 11q23 region. In addition, secondary acute lymphocytic leukemias (involving 11q23) have also been associated with prior epipodophyllotoxin exposure.