Agaliotis D P, Ballester O F, Mattox T, Hiemenz J W, Fields K K, Zorsky P E, Goldstein S C, Perkins J B, Rosen R M, Elfenbein G J
Division of Bone Marrow Transplantation, H. Lee Moffitt Cancer Center, University of South Florida, Tampa, USA.
Am J Med Sci. 1997 Nov;314(5):292-8. doi: 10.1097/00000441-199711000-00004.
The objective of this study was to evaluate nephrotoxicity in adult patients treated with high-dose ifosfamide, carboplatin, and etoposide followed by autologous stem cell transplantation. We conducted a retrospective analysis of clinical and laboratory data from 131 patients with various malignancies who received treatment with escalating doses of ifosfamide, carboplatin, and etoposide followed by autologous stem cell transplantation as part of a phase I/II therapeutic trial. Abnormalities in glomerular filtration were evaluated by measuring peak creatinine levels and tubular dysfunction by the lowest recorded serum levels of potassium, magnesium, and bicarbonate, at different time periods after administration of ifosfamide, carboplatin, and etoposide, and after autologous stem cell transplantation. For the entire group of 131 patients, peak creatinine levels were > 1.5 mg/dL but < 3.0 mg/dL in 37% and levels were > 3.0 mg/dL in 11% at some time during their hospital stay. At the time of discharge, creatinine levels were 1.6 mg/dL to 3.0 mg/dL in 25% of patients and were > 3 mg/dL in 5%. Immediately after high-dose therapy, peak creatinine levels were significantly higher in patients receiving higher doses of ifosfamide compared to those receiving lower doses (P < 0.00001) and those receiving intermediate doses (P < 0.005). There was a dramatic decrease in serum bicarbonate, potassium, and magnesium levels immediately after chemotherapy, and they remained significantly decreased throughout the patient's hospital stay, despite massive replacement efforts (P ranging between < 0.008 and < 0.001). This is the largest adult population study documenting the incidence and severity of ifosfamide/carboplatin/etoposide-associated acute nephrotoxicity. Renal dysfunction was dose related and reversible in the majority of patients.
本研究的目的是评估接受大剂量异环磷酰胺、卡铂和依托泊苷治疗后进行自体干细胞移植的成年患者的肾毒性。我们对131例患有各种恶性肿瘤的患者的临床和实验室数据进行了回顾性分析，这些患者作为I/II期治疗试验的一部分，接受了递增剂量的异环磷酰胺、卡铂和依托泊苷治疗，随后进行自体干细胞移植。通过测量肌酐峰值水平评估肾小球滤过异常，通过记录异环磷酰胺、卡铂和依托泊苷给药后以及自体干细胞移植后不同时间段血清钾、镁和碳酸氢盐的最低水平评估肾小管功能障碍。在131例患者的整个队列中，37%的患者肌酐峰值水平>1.5mg/dL但<3.0mg/dL，11%的患者在住院期间的某个时间肌酐水平>3.0mg/dL。出院时，25%的患者肌酐水平为1.6mg/dL至3.0mg/dL，5%的患者肌酐水平>3mg/dL。高剂量治疗后，接受高剂量异环磷酰胺的患者肌酐峰值水平显著高于接受低剂量的患者（P<0.00001）和接受中等剂量的患者（P<0.005）。化疗后血清碳酸氢盐、钾和镁水平立即显著下降，尽管进行了大量补充，但在患者住院期间一直显著低于正常水平（P值在<0.008至<0.001之间）。这是记录异环磷酰胺/卡铂/依托泊苷相关急性肾毒性发生率和严重程度的最大规模的成年人群研究。大多数患者的肾功能障碍与剂量相关且可逆转。
