Maddox A M, Keating M J, Freireich E J, Haddox M K
Division of Hematology/Oncology, University of Texas Medical School, Houston.
Chemotherapy. 1988;34(5):419-29. doi: 10.1159/000238602.
Eight patients who had refractory leukemia and 1 patient with refractory multiple myeloma were treated with the polyamine biosynthesis inhibitors methylgloxal bis(guanylhydrazone) (MGBG) and difluoromethylornithine (DFMO). After the first dose of MGBG there was an increase in polyamine content in the mononuclear cells of both the peripheral blood and the bone marrow despite the administration of DFMO in all patients with leukemia. Putrescine levels increased in the mononuclear cells of all patients, cellular spermidine levels increased in 4 and cellular spermine levels increased in 5 patients. The cellular polyamine levels remained elevated above the pretreatment levels for up to 1 week in some patients. Subsequent treatment with MGBG, administered after 1-2 weeks of DFMO treatment, also promoted increases in mononuclear cell polyamine concentrations. Since enhanced tumor cell uptake of MGBG after DFMO priming is hypothesized to be dependent on a decrease in cellular polyamine levels, the increase in cellular polyamines after MGBG has important implications for the scheduling of this drug combination. From these observations, withholding MGBG until DFMO treatment has produced a decrease in tumor cell polyamine concentrations would be the schedule most likely to enhance the uptake of MGBG.
8例难治性白血病患者和1例难治性多发性骨髓瘤患者接受了多胺生物合成抑制剂甲基乙二醛双（脒腙）（MGBG）和二氟甲基鸟氨酸（DFMO）治疗。在首次给予MGBG后，尽管所有白血病患者都使用了DFMO，但外周血和骨髓单核细胞中的多胺含量仍有所增加。所有患者单核细胞中的腐胺水平均升高，4例患者的细胞亚精胺水平升高，5例患者的细胞精胺水平升高。在一些患者中，细胞多胺水平在长达1周的时间内一直高于预处理水平。在DFMO治疗1 - 2周后给予MGBG进行后续治疗，也促进了单核细胞多胺浓度的增加。由于推测DFMO预处理后MGBG在肿瘤细胞中的摄取增强依赖于细胞多胺水平的降低，MGBG给药后细胞多胺的增加对这种药物联合方案的安排具有重要意义。从这些观察结果来看，在DFMO治疗使肿瘤细胞多胺浓度降低之前不给予MGBG，可能是最有可能增强MGBG摄取的方案。
