Department of Gastroenterology, Tokyo Women's Medical University, Shinjukuku, Tokyo, Japan.
Jpn J Clin Oncol. 2010 Apr;40(4):360-4. doi: 10.1093/jjco/hyp176. Epub 2010 Jan 18.
Long-term hemodialysis is considered to be a significant risk factor for cancer, but little is known about the use of oxaliplatin in patients on chronic hemodialysis. A 58-year-old man on chronic hemodialysis was treated for unresectable rectal cancer with synchronous hepatic metastasis by FOLFOX6 therapy with therapeutic drug monitoring. Plasma levels of total platinum, ultrafiltrate (free) platinum and 5-fluorouracil were monitored from the start of oxaliplatin administration to 120 h after the end of oxaliplatin infusion. Pharmacokinetic data of free platinum showed a bimodal pattern, decreased rapidly during the first dialysis and subsequently rose until 48 h after oxaliplatin infusion. The free platinum area under the curve was 15.7-18.9 microg h/ml when 40 mg/m(2) of oxaliplatin was administered, which was comparable to the area under the curve at 85 mg/m(2) in patient with normal renal function. The total platinum level reached a peak immediately before dialysis and gradually decreased. The 5-fluorouracil level decreased rapidly after the start of dialysis and remained constant during the continuous infusion of 5-fluorouracil. Tumor response was judged to be stable disease for >6 months, and no peripheral neuropathy or other toxicity was observed even after 11 courses. FOLFOX6 therapy with reduced dose of oxaliplatin had been safely performed for >6 months without any severe toxicity. The serum levels of free platinum showed bimodal pattern, and this second peak increased the area under the curve of free platinum. This pattern seems to be unique in patients on hemodialysis.
长期血液透析被认为是癌症的一个重要危险因素,但对于慢性血液透析患者使用奥沙利铂的情况知之甚少。一名 58 岁的男性因不可切除的直肠癌症合并同步肝转移,接受 FOLFOX6 治疗,同时进行治疗药物监测。从奥沙利铂给药开始到奥沙利铂输注结束后 120 小时,监测总铂、超滤(游离)铂和 5-氟尿嘧啶的血浆水平。游离铂的药代动力学数据呈双峰模式,在第一次透析期间迅速下降,随后在奥沙利铂输注结束后 48 小时上升。当给予 40mg/m(2)的奥沙利铂时,游离铂 AUC 为 15.7-18.9 microg h/ml,与肾功能正常患者 85mg/m(2)的 AUC 相当。总铂水平在透析前达到峰值,然后逐渐下降。5-氟尿嘧啶水平在透析开始后迅速下降,并在 5-氟尿嘧啶持续输注期间保持稳定。肿瘤反应被判断为稳定疾病>6 个月,即使在 11 个疗程后,也没有观察到周围神经病变或其他毒性。用减少剂量的奥沙利铂进行的 FOLFOX6 治疗已经安全地进行了>6 个月,没有任何严重的毒性。游离铂的血清水平呈双峰模式,第二个峰值增加了游离铂的 AUC。这种模式在血液透析患者中似乎是独特的。