Scheving L E, Burns E R, Halberg F, Pauly J E
Chronobiologia. 1980 Jan-Mar;7(1):33-40.
When cyclophosphamide, 1-beta-D-arabinofuranosylcytosine, vincristine, methylprednisolone (P) and cis-diamminedichloroplatinum (CP) were administered to mice previously given injections of 4.5 or 5 million L1210 leukemia cells, the effectiveness of the 5-drug combination was influenced by the stage of the circadian system at the time of injection. By applying what we refer to as the chronobiological approach (timed treatment), in comparison with a homeostatic (time unqualified) approach, fewer deaths and less weight loss were found, as the result probably of lower drug toxicity. Despite a cure rate that ranged from 24 to 48% as a function of CP timing in the first study, the overall acute drug toxicity (ranging from 20 to 76%) was unacceptable as a treatment protocol. In a second study, by lowering dosages of all drugs but still administering the drugs in a chronobiological manner, death due to acute drug toxicity was reduced to zero while the percentage of cures ranged from 44 to 88% in animals treated with P at different circadian stages. In both studies the homeostatic approach was unsatisfactory because of overwhelming drug toxicity.
当给预先注射了450万或500万L1210白血病细胞的小鼠施用环磷酰胺、1-β-D-阿拉伯呋喃糖基胞嘧啶、长春新碱、甲泼尼龙（P）和顺二氨二氯铂（CP）时，五药联合的有效性受注射时昼夜节律系统阶段的影响。通过应用我们所谓的时间生物学方法（定时治疗），与稳态（无时间限定）方法相比，发现死亡数更少且体重减轻更少，这可能是药物毒性较低的结果。尽管在第一项研究中治愈率根据CP给药时间在24%至48%之间，但作为一种治疗方案，总体急性药物毒性（在20%至76%之间）是不可接受的。在第二项研究中，通过降低所有药物的剂量但仍以时间生物学方式给药，急性药物毒性导致的死亡降至零，而在不同昼夜节律阶段接受P治疗的动物中治愈率在44%至88%之间。在两项研究中，稳态方法都因药物毒性过大而不尽人意。
