Department of Pharmacy, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Cancer Chemother Pharmacol. 2012 Jun;69(6):1537-44. doi: 10.1007/s00280-012-1860-8. Epub 2012 Mar 22.
In the present study, the time-concentration profile of platinum (Pt) in plasma was compared to that of serum cystatin C (Cys C) in Japanese esophageal cancer patients receiving perioperative cisplatin-based chemotherapy.
Five male and one female patients receiving 2 successive cycles of cisplatin-based chemotherapy combined with 5-fluorouracil, the treatment for esophageal squamous cell carcinoma, participated in this study. The pharmacokinetic parameters in each patient were calculated from the individual plasma Pt concentration-time curve after intravenous infusion of cisplatin using the one-compartment model.
Within a week of starting the first cycle of chemotherapy, serum Cys C concentrations increased in all patients from 122.6 to 143.0%, subsequently returning to baseline levels in approximately 10 days. A similar increase in serum Cys C levels also occurred during the second treatment cycle. However, no increase in serum creatinine levels was observed during either treatment cycle. In addition, the concentration of plasma Pt 2 days after treatment in the first and second cycles did not correlate with those of either serum Cys C or creatinine. Finally, the half-life of Pt in plasma during the first treatment cycle was not significantly different from that in the second cycle.
These findings suggest that concentration fluctuations in serum Cys C are unlikely to correlate with Pt elimination from the plasma and that renal function estimates based on serum Cys C concentration might be underestimated during perioperative cisplatin-based chemotherapy for esophageal cancer.
本研究比较了日本接受围手术期顺铂为基础化疗的食管癌患者血浆中铂(Pt)的时间-浓度曲线与血清胱抑素 C(Cys C)的时间-浓度曲线。
5 名男性和 1 名女性患者接受了 2 个周期的顺铂为基础化疗联合 5-氟尿嘧啶治疗食管鳞状细胞癌。每位患者的药代动力学参数均通过静脉注射顺铂后个体血浆 Pt 浓度-时间曲线采用单室模型计算。
在第一个化疗周期开始的一周内,所有患者的血清 Cys C 浓度从 122.6%增加到 143.0%,随后在大约 10 天内恢复到基线水平。在第二个治疗周期中,也观察到血清 Cys C 水平的类似增加。然而,在两个治疗周期中均未观察到血清肌酐水平的升高。此外,在第一和第二周期治疗后第 2 天,血浆 Pt 的浓度与血清 Cys C 或肌酐的浓度均无相关性。最后,第一治疗周期中血浆 Pt 的半衰期与第二周期无显著差异。
这些发现表明,血清 Cys C 浓度的波动不太可能与血浆中 Pt 的消除相关,并且在食管癌围手术期顺铂为基础化疗期间,基于血清 Cys C 浓度的肾功能估计可能被低估。