The Impact of Concomitant Medication Use on Patient Eligibility for Phase I Cancer Clinical Trials
The Impact of Concomitant Medication Use on Patient Eligibility for Phase I Cancer Clinical Trials
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DOI：
10.7150/jca.4714
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发表时间：
2012-01-01
影响因子：
3.9
通讯作者：
Von Hoff, Daniel D.
中科院分区：
文献类型：
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作者：
Borad, Mitesh J.;Curtis, Kelly K.;Von Hoff, Daniel D.
合并用药（CM）的使用可能导致I期癌症临床试验不合格，因为担心潜在的CM-研究药物相互作用或研究药物吸收的改变。很少有研究检查CM使用对试验合格性的影响。方法：我们回顾了274例患者在一个单一的学术机构的I期试验的记录。记录人口统计学、CM身份和类别、CM停药、原因和CM替代发生率。记录CM-研究药物细胞色素P450（CYP）酶相互作用。使用描述性统计进行统计分析。结果：274名患者中有273名（99.6%，95%置信区间[CI] 98.9-100%）服用CM，每位患者的中位数为8 CM（范围0 - 42）。67例病例发生CM停药（25%，95% CI 19-30%）。停药的最常见CM类别为草药（17例，25%，95% CI 16-37%）和质子泵抑制剂（15例，22%，95% CI 12-32%）。CM停药原因为：方案禁止（32例，48%，95% CI 36-60%）;潜在CM-研究药物相互作用（25例，37%，95% CI 26-49%）;其他（10例，15%，95% CI 6-23%）。在122例病例中观察到潜在的CM-研究药物相互作用（45%，95% CI 39-50%）。CM在52例病例中可能微弱降低研究药物代谢（43%，95% CI 34-51%），在17例病例中可能强烈降低研究药物代谢（14%，95% CI 8-20%）。在39例病例中，研究药物可能微弱降低CM代谢（32%，95% CI 24-40%），在28例病例中可能强烈降低CM代谢（23%，95% CI 15-30%）。36/67例（54%，95% CI 41-66%）病例发生CM替代，其中CM停药以允许最终参与临床试验。总体而言，在2例病例中（0.7%，95% CI 0.1-2.6%），患者不符合方案要求，因为CM无法停药或替代。结论：这项研究强调了在I期临床试验中登记的癌症患者中合并用药的高患病率。大多数患者确实符合试验合格性标准，但需谨慎替换和停用CM。CM停药的最常见原因是方案禁止。最常见的停药药物是草药、质子泵抑制剂、选择性5-羟色胺再摄取抑制剂、抗抑郁药和非甾体抗炎药。
Concomitant medication (CM) use may result in Phase I cancer clinical trial ineligibility due to concern for potential CM-investigational drug interactions or alteration of investigational drug absorption. Few studies have examined the impact of CM use on trial eligibility. Methods: We reviewed records of 274 patients on Phase I trials at a single academic institution. Demographics, CM identities and classes, CM discontinuation, reasons, and incidence of CM substitution were recorded. CM-investigational drug cytochrome P450 (CYP) enzyme interactions were documented. Statistical analysis was performed using descriptive statistics. Results: 273 of 274 patients (99.6%, 95% confidence interval [CI] 98.9-100%) took CM, with a median of 8 CM per patient (range 0 - 42). CM discontinuation occurred in 67 cases (25%, 95% CI 19-30%). The most common CM classes discontinued were herbal (17 cases, 25%, 95% CI 16-37%) and proton pump inhibitors (15 cases, 22%, 95% CI 12-32%). CM discontinuation reasons were: protocol prohibition (32 cases, 48%, 95% CI 36-60%); potential CM-investigational drug interaction (25 cases, 37%, 95% CI 26-49%); other (10 cases, 15%, 95% CI 6-23%). A potential CM-investigational drug CYP interaction was noted in 122 cases (45%, 95% CI 39-50%). CM potentially weakly decreased investigational drug metabolism in 52 cases (43%, 95% CI 34-51%), and potentially strongly decreased investigational drug metabolism in 17 cases (14%, 95% CI 8-20%). Investigational drug potentially weakly decreased CM metabolism in 39 cases (32%, 95% CI 24-40%), and potentially strongly decreased CM metabolism in 28 cases (23%, 95% CI 15-30%). CM substitution occurred in 36/67 cases (54%, 95% CI 41-66%) where CM were discontinued to allow for eventual participation in clinical trials. Overall in 2 cases (0.7%, 95% CI 0.1-2.6%), patients were protocol ineligible because CM could not be discontinued or substituted. Conclusions: This study highlights the high prevalence of concomitant medication use among cancer patients enrolled in phase I clinical trials. Most patients did meet trial eligibility criteria with careful substitution and discontinuation of CM. The most common reason for discontinuation of CM was protocol prohibition. The most common medications discontinued were herbal, proton pump inhibitors, selective serotonin reuptake inhibitor anti-depressants, and non-steroidal anti-inflammatory drugs.