THE FIRST CLINICAL PILOT-STUDY OF ROQUINIMEX (LINOMIDE(R)) IN CANCER-PATIENTS WITH SPECIAL FOCUS ON IMMUNOLOGICAL EFFECTS

Roquinimex (Linomide(R)) has been demonstrated to suppress tumor growt h in animal models. The effect is at least in part related to enhanced numbers and activity of natural killer (NK) cells. In this clinical p ilot study, roquinimex was given at increasing doses (0.05 mg/kg to 0. 6 mg/kg) to 13 patients (performance status 0-3) with various malignan t disorders. Immunology parameters were followed and side effects were observed during the study. The plasma pharmacokinetics of roquinimex was studied at the 0.2 mg/kg dose level. The clinical side effects wer e dominated by musculoskeletal discomfort, nausea, and pain. No signif icant hematological or biochemical toxicity was observed. Pharmacokine tic analysis at the 0.2 mg/kg dose level revealed a C-max of 4.0 mu mo l/L at t(max) of 1.2 hr and an elimination half-life of 42 hr. Increas ed numbers of phenotypic NK cells, activated T (DR(+)CD4(+)) cells, an d monocytes were observed after administration of roquinimex compared with pretreatment values. Roquinimex seems to be an active immunomodul ator with manageable toxicity. Further exploration of therapeutic effi cacy is warranted.