See W A, Crist S A, Boileau M A, Williams R D
Department of Urology, University of Iowa, Iowa City 52242.
Cancer Res. 1991 Mar 1;51(5):1373-7.
An implantable rat bladder tumor model using the rat transitional carcinoma cell line 4909 was used to evaluate the effect of single-dose, preoperative, systemic chemotherapy on the risk of intravesical tumor implantation. To simulate the clinical setting in which drug levels would be present in both the tumor and the site of implantation, both tumor donor animals and tumor recipients were given a single dose of cyclophosphamide (CY) 1 h prior to tumor harvest and implantation. This protocol resulted in a significant reduction in the incidence of tumor implantation, in tumor volume, and in the incidence of nodal metastases relative to control animals. Dose-response experiments demonstrated that 10 of 139 (7%) animals treated with single doses of CY ranging from 2.5-100 mg/kg developed tumors as compared to 46 of 66 (70%) animals with tumors in the control groups (P less than 0.001). CY doses below 2.5 mg/kg were associated with an increased incidence of tumor implantation (19 of 45, 42%). No lethal toxicity was seen at doses of 50 mg/kg or less. Peak antitumor activity occurred when the CY was administered 1 h prior to tumor implantation as compared to 48 or 24 h before or 1 or 24 h after tumor implantation. Preoperative "chemoprophylaxis" may be an effective strategy for preventing bladder tumor recurrences resulting from tumor implantation.
使用大鼠移行癌细胞系4909建立了可植入的大鼠膀胱肿瘤模型，以评估单剂量术前全身化疗对膀胱内肿瘤种植风险的影响。为模拟肿瘤和种植部位均存在药物水平的临床情况，在肿瘤采集和种植前1小时，给肿瘤供体动物和肿瘤受体动物均单剂量给予环磷酰胺（CY）。与对照动物相比，该方案使肿瘤种植的发生率、肿瘤体积和淋巴结转移的发生率显著降低。剂量反应实验表明，139只接受2.5-100mg/kg单剂量CY治疗的动物中有10只（7%）发生肿瘤，而对照组66只患肿瘤动物中有46只（70%）发生肿瘤（P<0.001）。低于2.5mg/kg的CY剂量与肿瘤种植发生率增加相关（45只中有19只，42%）。50mg/kg及以下剂量未见致死毒性。与在肿瘤种植前48或24小时、或肿瘤种植后1或24小时给予CY相比，在肿瘤种植前1小时给予CY时抗肿瘤活性达到峰值。术前“化学预防”可能是预防因肿瘤种植导致膀胱肿瘤复发的有效策略。
