Abb J, Netzel B, Rodt H V, Thierfelder S
Cancer Res. 1978 Jul;38(7):2157-9.
Hematological and immunosuppressive effects of various single doses of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) were evaluated in the preclinical canine model. Immune function appeared not to be impaired by treatment with CCNU, but severe myelotoxicity contributed to the death of 3 of 4 dogs given 10 mg CCNU per kg and 5 of 5 dogs given 15 mg CCNU per kg within 10 days after drug administration. Infusions of autologous bone marrow protected 6 of 6 dogs receiving 15 mg CCNU per kg and 6 of 6 dogs receiving 20 mg CCNU per kg from lethal marrow failure. Dogs given 30 mg CCNU per kg and autologous marrow died within 7 days from severe gastrointestinal toxicity. We conclude that autologous bone marrow support may allow the use of high-dose CCNU regimens and thereby increase its therapeutic efficacy in the treatment of advanced cancer.
在临床前犬模型中评估了不同单剂量的1-(2-氯乙基)-3-环己基-1-亚硝基脲（CCNU）的血液学和免疫抑制作用。CCNU治疗似乎未损害免疫功能，但严重的骨髓毒性导致每千克给予10mg CCNU的4只犬中有3只以及每千克给予15mg CCNU的5只犬中有5只在给药后10天内死亡。自体骨髓输注保护了每千克接受15mg CCNU的6只犬中的6只以及每千克接受20mg CCNU的6只犬中的6只免于致命的骨髓衰竭。每千克给予30mg CCNU并接受自体骨髓的犬在7天内死于严重的胃肠道毒性。我们得出结论，自体骨髓支持可能允许使用高剂量CCNU方案，从而提高其在晚期癌症治疗中的疗效。
