Milano G, Troger V, Courdi A, Fontana X, Chauvel P, Lagrange J L
Centre Antoine-Lacassagne, Nice, France.
Cancer Chemother Pharmacol. 1990;27(1):55-9. doi: 10.1007/BF00689277.
A total of 25 patients with inoperable cervical cancer were treated by daily radiotherapy (2 Gy); sensitisation was obtained by administration of 5 mg cisplatin 30 min before each irradiation session. The total cumulative dose of cisplatin varied between 50 and 150 mg. A complete kinetic profile (0-24 h) of platinum (Pt) was established after the first dose and at the end of treatment for 22 patients. Pt was quantified by atomic absorption spectrophotometry using Zeeman-effect background correction for trace analysis. The total Pt AUC0-24h increased from 1.53 +/- 0.77 to 7 +/- 3.55 micrograms.h.ml-1 between the start and the end of treatment (P less than 0.001). Ultrafilterable Pt (Pt UF) rose from 0.079 +/- 0.038 to 0.138 +/- 0.095 microgram.h.ml-1 (P less than 0.01). Elimination half-lives were unchanged for total Pt but rose for Pt UF; these kinetic modifications in Pt UF did not correlate with any significant change in individual serum creatinine levels. No clear correlation was found between the cumulative cisplatin dose and tumor levels measured in 13 patients, and the tumor cisplatin dose did not correlate with response to treatment. Patients with hematological toxicity were characterised by an increase in their residual Pt UF level during treatment. Overall, our findings strengthen the notion of Pt UF kinetic variability during repeated treatment.
共有25例无法手术的宫颈癌患者接受了每日放疗（2 Gy）；在每次放疗前30分钟给予5 mg顺铂以实现增敏。顺铂的总累积剂量在50至150 mg之间。在首次给药后及治疗结束时，对22例患者建立了铂（Pt）完整的动力学曲线（0 - 24小时）。使用塞曼效应背景校正的原子吸收分光光度法对痕量分析的Pt进行定量。治疗开始时到结束时，总Pt AUC0 - 24h从1.53±0.77微克·小时·毫升⁻¹增加到7±3.55微克·小时·毫升⁻¹（P＜0.001）。可超滤铂（Pt UF）从0.079±0.038微克·小时·毫升⁻¹升至0.138±0.095微克·小时·毫升⁻¹（P＜0.01）。总Pt的消除半衰期未变，但Pt UF的消除半衰期延长；Pt UF的这些动力学改变与个体血清肌酐水平的任何显著变化均无相关性。在13例患者中，未发现累积顺铂剂量与肿瘤水平之间有明确相关性，且肿瘤顺铂剂量与治疗反应也无相关性。血液学毒性患者的特征是治疗期间其残余Pt UF水平升高。总体而言，我们的研究结果强化了重复治疗期间Pt UF动力学变异性的概念。
