环磷酰胺对小鼠淋巴瘤对数杀灭动力学与“治愈性”化疗策略

Log kill kinetics and "curative" chemotherapy strategy of cyclophosphamide on mice malignant lymphoma

目的 :探讨化疗对肿瘤细胞对数杀灭效果定量评价对肿瘤“治愈性”化疗策略的指导意义。方法 :移植津白Ⅱ号小鼠淋巴瘤 (L TA2 ) ,直径达 10mm时开始环磷酰胺 (CTX) 5 0mg/kg腹腔内注射 ,每 6天 1次 ,共 3次治疗 ;复发瘤以大剂量CTX(HD CTX) 10 0mg/kg腹腔内注射 ,每 6天 1次 ,共 3次解救。计算治疗后隔日体积与细胞对数。 结果 :每次治疗杀灭对数在0～ 3.0范围波动明显 ,初治对数杀灭呈递增趋势 ,部分缓解复发瘤对HD CTX高度敏感 ,完全缓解后复发瘤明显耐药 ,且非足程治疗肿瘤仍复发。结论 :一定剂量药物并非按恒定比例 (对数 )杀灭肿瘤细胞 ,定量评价每次化疗对肿瘤细胞对数杀灭效果和治疗后残瘤细胞负荷 ,对肿瘤“治愈性”化疗策略的制订和调整有重大指导意义。

Objective:To investigate the guiding significance of the log kill quantitative evaluation of cancer chemotherapy to 'curative' chemotherapy strategy.Methods:The primary treatment was performed by cyclophosphamide(CTX) 50 mg/kg intraperitoneal injection,per six days for 3 times when the diameter of the transplantable L TA 2 mass growed to 10 mm and the relapsed tumors were saved by a high dose of CTX(HD CTX) 100 mg/kg intraperitoneal injection,per six days for 3 times.The volume and the cell log of the mass were evaluated quantitatively every other day.Results:The log kill effect of each treatment varied obviously in 0 to 3 log range.The log kill effect increased progressively in the primary therapy,the relapsing tumors after the partial remission(PR) were very sensitive to the HD CTX saving and the relapsing tumors after the complete remission(CR) were obviously resistant,but the residual tumor would still relapse once the treatment was not continued after the CR was acquired.Conclusions:A given dose of drug will kill a very different fraction of a given tumor cell population.It is essential to make the quantitative evaluation of log kill effect per treatment on a given tumor and of the post treatment residual body burden of tumor so as to adjust 'curative' cancer chemotherapy strategies.