PDF(Pubmed)
Abstract：
BACKGROUND: The proportion of patients with breast cancer and obesity is increasing. While the therapeutic landscape of breast cancer has been expanding, we lack knowledge about the potential differential efficacy of most drugs according to the body mass index (BMI). Here, we conducted a systematic review on recent clinical drug trials to document the dosing regimen of recent drugs, the reporting of BMI and the possible exclusion of patients according to BMI, other adiposity measurements and/or diabetes (leading comorbidity of obesity). We further explored whether treatment efficacy was evaluated according to BMI.
METHODS: A search of Pubmed and ClinicalTrials.gov was performed to identify phase I-IV trials investigating novel systemic breast cancer treatments. Dosing regimens and exclusion based on BMI, adiposity measurements or diabetes, documentation of BMI and subgroup analyses according to BMI were assessed.
RESULTS: 495 trials evaluating 26 different drugs were included. Most of the drugs (21/26, 81%) were given in a fixed dose independent of patient weight. BMI was an exclusion criterion in 3 out of 495 trials. Patients with diabetes, the leading comorbidity of obesity, were excluded in 67/495 trials (13.5%). Distribution of patients according to BMI was mentioned in 8% of the manuscripts, subgroup analysis was performed in 2 trials. No other measures of adiposity/body composition were mentioned in any of the trials. Retrospective analyses on the impact of BMI were performed in 6 trials.
CONCLUSIONS: Patient adiposity is hardly considered as most novel drug treatments are given in a fixed dose. BMI is generally not reported in recent trials and few secondary analyses are performed. Given the prevalence of patients with obesity and the impact obesity can have on pharmacokinetics and cancer biology, more attention should be given by investigators and study sponsors to reporting patient\'s BMI and evaluating its impact on treatment efficacy and toxicity.
METHODS: A search of Pubmed and ClinicalTrials.gov was performed to identify phase I-IV trials investigating novel systemic breast cancer treatments. Dosing regimens and exclusion based on BMI, adiposity measurements or diabetes, documentation of BMI and subgroup analyses according to BMI were assessed.
RESULTS: 495 trials evaluating 26 different drugs were included. Most of the drugs (21/26, 81%) were given in a fixed dose independent of patient weight. BMI was an exclusion criterion in 3 out of 495 trials. Patients with diabetes, the leading comorbidity of obesity, were excluded in 67/495 trials (13.5%). Distribution of patients according to BMI was mentioned in 8% of the manuscripts, subgroup analysis was performed in 2 trials. No other measures of adiposity/body composition were mentioned in any of the trials. Retrospective analyses on the impact of BMI were performed in 6 trials.
CONCLUSIONS: Patient adiposity is hardly considered as most novel drug treatments are given in a fixed dose. BMI is generally not reported in recent trials and few secondary analyses are performed. Given the prevalence of patients with obesity and the impact obesity can have on pharmacokinetics and cancer biology, more attention should be given by investigators and study sponsors to reporting patient\'s BMI and evaluating its impact on treatment efficacy and toxicity.
摘要：
背景：乳腺癌和肥胖患者的比例正在增加。虽然乳腺癌的治疗前景一直在扩大，根据体重指数（BMI），我们缺乏对大多数药物潜在疗效差异的了解。这里,我们对最近的临床药物试验进行了系统评价，以记录最近药物的给药方案，BMI的报告和根据BMI可能排除的患者，其他肥胖测量和/或糖尿病（肥胖的主要合并症）。我们进一步探讨了是否根据BMI评估治疗效果。
方法：对Pubmed和ClinicalTrials.gov进行了检索，以确定研究新型全身性乳腺癌治疗的I-IV期试验。基于BMI的给药方案和排除，肥胖测量或糖尿病，评估了BMI的记录和根据BMI进行的亚组分析。
结果：495项试验评估了26种不同的药物。大多数药物（21/26，81%）以固定剂量给予，与患者体重无关。在495项试验中，有3项是排除标准。糖尿病患者,肥胖的主要合并症，在67/495项试验中被排除（13.5%）。8％的手稿中提到了根据BMI分布的患者，在2项试验中进行了亚组分析.在任何试验中都没有提到肥胖/身体成分的其他测量。在6项试验中对BMI的影响进行了回顾性分析。
结论：患者肥胖几乎不被考虑，因为大多数新型药物治疗是以固定剂量给予的。在最近的试验中通常没有报道BMI，并且很少进行二次分析。鉴于肥胖患者的患病率以及肥胖对药代动力学和癌症生物学的影响，研究者和研究赞助者应更多关注报告患者的BMI并评估其对治疗疗效和毒性的影响.
方法：对Pubmed和ClinicalTrials.gov进行了检索，以确定研究新型全身性乳腺癌治疗的I-IV期试验。基于BMI的给药方案和排除，肥胖测量或糖尿病，评估了BMI的记录和根据BMI进行的亚组分析。
结果：495项试验评估了26种不同的药物。大多数药物（21/26，81%）以固定剂量给予，与患者体重无关。在495项试验中，有3项是排除标准。糖尿病患者,肥胖的主要合并症，在67/495项试验中被排除（13.5%）。8％的手稿中提到了根据BMI分布的患者，在2项试验中进行了亚组分析.在任何试验中都没有提到肥胖/身体成分的其他测量。在6项试验中对BMI的影响进行了回顾性分析。
结论：患者肥胖几乎不被考虑，因为大多数新型药物治疗是以固定剂量给予的。在最近的试验中通常没有报道BMI，并且很少进行二次分析。鉴于肥胖患者的患病率以及肥胖对药代动力学和癌症生物学的影响，研究者和研究赞助者应更多关注报告患者的BMI并评估其对治疗疗效和毒性的影响.
