Phase I study in malignancy of LS 2616, a new immunomodulator: methodological considerations

LS 2616 (Linomide) is a new immunomodulator that enhances natural killer (NK)-cell activity, delayed-type hypersensitivity reaction, mitogen responsiveness of T cells, and antibody production. It suppresses tumor growth and reduces metastases in animal experiments. In a phase I clinical trial, the maximal tolerated dose will not necessarily be the maximally effective dose, so both effect and toxicity parameters have to be monitored. Because of the pleiotropic function of the drug, several biological responses have to be analyzed. Furthermore, different malignancies are associated with different immunologic disturbances both qualitatively and quantitatively, necessitating the use of normal controls and baseline assessments as well as a range of different malignancies. The pharmacokinetic features will differ from the kinetics of the biological responses, and thus both drug concentration and effect parameters will be followed over time. Repeated doses will give information needed for tailoring of optimal schedules for administration.