Single-Dose Preoperative Systemic Cyclophosphamide for the Prevention of Bladder Tumor Implantation in F344 Rats

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 < 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.