Tanaka Toshikazu, Fujita Shoichi, Tanaka Noriko, Ooka Masaru, Okajima Shiro, Tanaka Noriaki
Tanaka Kitanoda Hospital.
Gan To Kagaku Ryoho. 2005 Jun;32(6):841-5.
The optimum dose of TS-1 for the treatment of peritoneally disseminated gastric cancer in a patient with chronic renal failure undergoing chronic dialysis was estimated by monitoring the blood concentrations of 5-FU and gimeracil (CDHP) [therapeutic drug monitoring (TDM)] during administration of TS-1. Immediately after dialysis, 50 mg or 40 mg of TS-1, corresponding to 50% and 40% of the standard dose (100mg for this patient), respectively, was administered orally once a day every other day, and TDM was conducted. Compared with the pharmacokinetic parameters of 5-FU at the time of the initial administration of 50 mg or 40 mg of TS-1 and that of cancer patients with normal renal function, the AUC shown in the administration of 40 mg was equivalent to that observed with a single safe dose of 100 mg in patients with normal renal function. Based on this observation, the daily TS-1 dose was set at 40 mg in this patient, and TS-1 treatment was started after confirming the absence of the accumulation of 5-FU or CDHP during repeated administrations. In this treatment protocol, TS-1 was administered 11 times at a daily dose of 40 mg every other day immediately after dialysis, followed by a rest. This .administration schedule was defined as one course. Under these conditions, the patient was treated on an outpatient basis, and the treatment could be safely continued without the development of any severe adverse events, such as myelosuppression.
在一名接受慢性透析的慢性肾衰竭患者中,通过在服用替吉奥(TS-1)期间监测5-氟尿嘧啶(5-FU)和吉美嘧啶(CDHP)的血药浓度[治疗药物监测(TDM)],估算出治疗腹膜播散性胃癌的TS-1最佳剂量。透析结束后,立即每隔一天口服一次TS-1,剂量分别为50mg或40mg,分别相当于标准剂量(该患者为100mg)的50%和40%,并进行TDM。将初始服用50mg或40mg TS-1时5-FU的药代动力学参数与肾功能正常的癌症患者进行比较,服用40mg时的曲线下面积(AUC)与肾功能正常患者单次安全剂量100mg时观察到的AUC相当。基于这一观察结果,该患者的TS-1每日剂量设定为40mg,并在确认重复给药期间5-FU或CDHP无蓄积后开始TS-1治疗。在该治疗方案中,透析结束后立即每隔一天以40mg的每日剂量服用TS-1 11次,然后休息。这种给药方案定义为一个疗程。在这些条件下,该患者为门诊治疗,且治疗可以安全地持续进行,未出现任何严重不良事件,如骨髓抑制。