van Berlo-van de Laar I R F, Brummelhuis W J, Imholz A L T, Schellens J H, Huitema A D R, Jansman F G A
Department of Clinical Pharmacy, Deventer Hospital, Deventer, The Netherlands.
Department of Clinical Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
J Clin Pharm Ther. 2018 Aug;43(4):574-577. doi: 10.1111/jcpt.12661. Epub 2018 Jan 5.
Oxaliplatin in combination with fluorouracil and folinic acid is one of the preferred chemotherapeutic options in the treatment of metastatic rectum cancer. However, oxaliplatin is contraindicated in patients with a creatinine clearance <30 mL/min and dosing guidelines in patients on haemodialysis have not been established.
A 77-year-old haemodialysis patient with metastatic rectum cancer was treated with FOLFOX and bevacizumab (oxaliplatin 70 mg/m , folinic acid 200 mg/m , 5-FU 340 mg/m bolus and 2040 mg/m continuous infusion during 44 hours and bevacizumab 5 mg/kg) every three weeks. Haemodialysis started immediately after infusion of oxaliplatin. The oxaliplatin dose was monitored by measuring free platinum ultrafiltrate concentrations. The AUC of free platinum plasma ultrafiltrate after cycles 1-3, respectively, was 24.3, 24.7 and 25.8 μg*h/mL. The C was, respectively, 1.3, 1.3 and 2.2 μg/mL. There was no accumulation of free platinum detectable. The patient experienced no toxicity, and after 3 cycles, the CT scan showed a decrease in the liver metastases after which hemihepatectomy and metastasectomy were performed without any complications. A CT scan 6 months after the surgery showed no new liver metastases. However, lymphatic metastasis was diagnosed for which palliative treatment was started.
Dosing oxaliplatin in a haemodialysis patient monitored by free platinum concentrations was effective, safe and feasible in clinical practice. Further research is needed to determine the best pharmacokinetic parameter or combination of parameters and corresponding target values to further optimize the oxaliplatin dose for the individual haemodialysis patient.
奥沙利铂联合氟尿嘧啶和亚叶酸钙是转移性直肠癌治疗的首选化疗方案之一。然而,肌酐清除率<30 mL/min的患者禁用奥沙利铂,且尚未确立血液透析患者的给药指南。
一名77岁的转移性直肠癌血液透析患者接受FOLFOX和贝伐单抗治疗(奥沙利铂70 mg/m²,亚叶酸钙200 mg/m²,5-氟尿嘧啶340 mg/m²静脉推注及2040 mg/m²持续输注44小时,贝伐单抗5 mg/kg),每三周一次。奥沙利铂输注后立即开始血液透析。通过测量游离铂超滤浓度监测奥沙利铂剂量。第1 - 3周期后游离铂血浆超滤的AUC分别为24.3、24.7和25.8 μg*h/mL。Cmax分别为1.3、1.3和2.2 μg/mL。未检测到游离铂蓄积。患者未出现毒性反应,3个周期后,CT扫描显示肝转移灶缩小,随后行半肝切除和转移灶切除,无任何并发症。术后6个月的CT扫描显示无新的肝转移。然而,诊断出有淋巴转移,开始进行姑息治疗。
在血液透析患者中通过游离铂浓度监测来给予奥沙利铂在临床实践中是有效、安全且可行的。需要进一步研究以确定最佳药代动力学参数或参数组合及相应的目标值,以进一步优化针对个体血液透析患者的奥沙利铂剂量。