The effect of BM 12.531 (azimexon) on natural killer cell activity in myeloma patients.
The 2-cyanaziridin derivative, azimexon (E), has previously been shown to have certain immunomodulatory properties. In particular, the induction of leukocytosis, the stimulation of delayed-type hypersensitivity reactions and the synergistic effect of azimexon and antibiotics in the control of lethal bacterial and fungal infections in mice prompted us to test azimexon as an adjuvant to chemotherapy in 14 myeloma patients. In a randomized double-blind cross-over study 3 X 600 mg of azimexon were added to one of two consecutive, identical chemotherapy courses consisting of melphalan/prednisone (MP) or vincristine/cyclophosphamide/melphalan/prednisone (VCMP). Chemotherapy was given during days 1-4 and azimexon or placebo were added on days 6, 10 and 14. Blood counts and natural killer (NK) cell testing were performed on days 0 and 21 of each course. With the exception of a transient taste irritation in two patients, azimexon caused no subjective side-effects. White blood cell counts were not altered by the drug; red blood cells and hemoglobin showed a borderline depression after azimexon. NK activities measured against three target cell lines (K562, IGR3, L1210) tended to increase after azimexon treatment. When added in vitro to NK assays azimexon caused a slight increase of NK activity at concentrations of 0.01-0.25 mu/ml, whereas concentrations above 1 microgram/ml were inhibitory. The increase of NK activity by azimexon was not due to the induction of interferon in the effector lymphocyte population.
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D001388:Aziridines / Q000494:pharmacology / Q000627:therapeutic use*; D001389:Azirines / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003520:Cyclophosphamide / Q000627:therapeutic use; D004311:Double-Blind Method; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects*; D007958:Leukocyte Count; D008558:Melphalan / Q000627:therapeutic use; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy*; D011241:Prednisone / Q000627:therapeutic use; D014750:Vincristine / Q000627:therapeutic use
D000276:Adjuvants, Immunologic; D001388:Aziridines; D001389:Azirines; C016866:azimexon; D014750:Vincristine; D003520:Cyclophosphamide; D008558:Melphalan; D011241:Prednisone