Drug Development Unit, Division of Clinical Studies, The Institute of Cancer Research/The Royal Marsden NHS Foundation Trust, Sutton, UK.
Oncology. 2012;83(4):177-82. doi: 10.1159/000341152. Epub 2012 Aug 7.
This study aimed to evaluate any correlations between baseline creatinine clearance and the development of grade 3/4 toxicities during treatment within oncology phase I trials of molecularly targeted agents where entry criteria mandate a serum creatinine of ≤ 1.5 × the upper limit of normal.
Documented toxicity and creatinine clearance (calculated by the Cockcroft-Gault formula) from all patients treated with molecularly targeted agents in the context of phase I trials within our centre over a 5-year period were analyzed.
Data from 722 patients were analyzed; 116 (16%) developed at least one episode of grade 3/4 toxicity. Patients who developed a late-onset (>1 cycle) grade 3/4 toxicity had a lower creatinine clearance than those who did not (82.69 ml/min vs. 98.97 ml/min; p = < 0.001).
Creatinine clearance (even when within normal limits) should be studied as a potential factor influencing late toxicities in the clinical trials of molecularly targeted anti-cancer drugs.
本研究旨在评估分子靶向药物 I 期临床试验中，入组标准规定血清肌酐≤1.5 倍正常值上限时，基线肌酐清除率与治疗期间发生 3/4 级毒性之间的相关性。
分析了本中心 5 年内 I 期试验中接受分子靶向药物治疗的所有患者的毒性和肌酐清除率（用 Cockcroft-Gault 公式计算）的记录数据。
共分析了 722 例患者的数据，其中 116 例（16%）发生了至少一次 3/4 级毒性。发生迟发性（>1 个周期）3/4 级毒性的患者肌酐清除率低于未发生毒性的患者（82.69ml/min 比 98.97ml/min；p<0.001）。
即使在正常值范围内，也应研究肌酐清除率（creatinine clearance）作为影响分子靶向抗癌药物临床试验中迟发性毒性的潜在因素。
