Antitumor and Toxic Effects of Combination Chemotherapy With Bleomycin and a Phenothiazine Anticalmodulin Agent1

Phenothiazines and structurally related calmodulin antagonists acted synergistically with blemycin in killing malignant cells in culture. For exploration of the potential clinical importance of this observation, the effects of administering the combination of chlorpromazine and bleomycin in vitro and in vivo against the transplantable B16 melanoma were studied. The toxicity of the combination to bone marrow and lungs was also determined. Combined chlorpromazine and bleomycin therapy reduced the concentration of chlorpromazine required to inhibit cellular growth of B16 melanoma cells by greater than half (25 vs. 60μM). Against the transplanted tumor, after 3 weeks of treatment the tumor sizes )in cubic millimeters) were 540 ± 100 (vehicle), 520 ± 120 (chlorpromazine), 170 ± 10 (bleomycin), and 80±20 (blemmycin + Chlorpromazine, P