AbstractPrevious reports have indicated that human urothelial cancer is more sensitive to combination radiation-cisplatin than to either treatment given alone and that the treatment schedule may be an important factor in determining the magnitude of tumor response. In the present study we have investigated the effect of timing and the sequence of combination“radiation-cisplatin”on human urothelial cancer grown in nude mice. Tumors were exposed to 1000 rod x-irradiation and received cisplatin treatment in the amount of 5 mg/kg once on each specified day before or after radiation. Best tumor responses, characterized by significant tumor growth delay and tumor regression, were observed when cisplatin was given on Day 3 and 6 postradiation. The present work has indicated that timing and sequence of treatments in the combination“radiation-cisplatin”are important factors in determining tumor response and may be of assistance in formulating the most effective clinical trials of urothelial cancer patients.