Simpson H W, Stoney P J
Br J Haematol. 1977 Mar;35(3):459-64. doi: 10.1111/j.1365-2141.1977.tb00607.x.
The toxicity of Melphalan to murine bone marrow was assessed by automated Coulter counts of femoral marrow nucleated cells. A significant dose-response slope (p less than 0.001) was shown and also a significant variation along the 24 h scale. With food available ad libitum and light from 06.00 to 18.00 hours, the minimum marrow depression occurred around 16.00 hours. Extrapolating these findings to human chemotherapy it would appear that prescription of the drug during the early part of the activity span (usually breakfast) will minimize marrow depression. This differs from a human study in which Melphalan was given at 'bedtime' as an adjuvant to mastectomy in breast carcinoma and in which there was leucopenia at some stage of treatment in all 103 patients. It is recommended that in future cancer therapy protocols test for circadian variability of white cell depression by varying treatment times systematically along the 24 h scale.
通过对股骨骨髓有核细胞进行自动库尔特计数，评估美法仑对小鼠骨髓的毒性。结果显示出显著的剂量反应斜率（p小于0.001），并且在24小时内也有显著变化。在随意进食且光照时间为06:00至18:00的情况下，骨髓抑制最低点出现在16:00左右。将这些发现外推至人类化疗，似乎在活动时间段的早期（通常是早餐时）给药可使骨髓抑制最小化。这与一项人类研究不同，在该研究中，美法仑作为乳腺癌乳房切除术的辅助药物在“就寝时间”给药，103例患者在治疗的某个阶段均出现白细胞减少。建议在未来的癌症治疗方案中，通过在24小时内系统地改变治疗时间来测试白细胞减少的昼夜变异性。
