Schenken L L, Hagemann R F, Burholt D R, Lesher S
J Natl Cancer Inst. 1976 Oct;57(4):943-9. doi: 10.1093/jnci/57.4.943.
We investigated the effects of cyclophosphamide, alone and in combination with a 1,000-R/week radiotherapy schedule, on the growth of solid P815X2 tumors in 12-week-old male DBA/2 mice. Single-dose treatments of 150 mg cyclophosphamide/kg were given to animals bearing tumors of different ages. Such treatment of young tumors resulted in proportionately greater degrees of regression and steeper regrowth curves than did treatment of older tumors. Although slopes of regrowth curves differed greatly, time to regrowth (to pretreatment size) was the same for all age classes of tumors. Graded weekly exposures of 50-250 mg/kg for 4 weeks resulted in dose-dependent increases in incidence of complete remission, duration of remission (time to regrowth), and mean animal life-spans. The combination of radiotherapy to the tumor and 75, 150, or 225 mg cyclophosphamide/kg/week resulted in better local tumor control than occurred with radiotherapy or the drug alone. However, a dose-dependent increase in radiosensitivity of the gastrointestinal mucosa included in radiotherapy fields was observed. A 3-week course of radiotherapy plus 75 mg cyclophosphamide/kg/week (which is tolerated by the mucosa) increased animal lifespans to 165% of those of controls.
我们研究了环磷酰胺单独使用以及与每周1000拉德的放射治疗方案联合使用，对12周龄雄性DBA/2小鼠体内实体P815X2肿瘤生长的影响。对患有不同年龄肿瘤的动物给予150毫克环磷酰胺/千克的单剂量治疗。与治疗较老的肿瘤相比，这种对年轻肿瘤的治疗导致了更大程度的消退和更陡峭的再生长曲线。尽管再生长曲线的斜率差异很大，但所有年龄段肿瘤的再生长时间（恢复到治疗前大小的时间）是相同的。每周给予50 - 250毫克/千克，持续4周的分级暴露导致完全缓解的发生率、缓解持续时间（再生长时间）和动物平均寿命呈剂量依赖性增加。对肿瘤进行放射治疗并联合75、150或225毫克环磷酰胺/千克/周，比单独进行放射治疗或使用药物能更好地控制局部肿瘤。然而，观察到放射治疗区域内胃肠道黏膜的放射敏感性呈剂量依赖性增加。为期3周的放射治疗加75毫克环磷酰胺/千克/周（黏膜可耐受）使动物寿命延长至对照组的165%。
