Mangoni Arduino A, Kichenadasse Ganessan, Rowland Andrew, Sorich Michael J
Department of Clinical Pharmacology, College of Medicine and Public Health, Flinders University and Flinders Medical Centre, Adelaide, Australia.
Flinders Centre for Innovation in Cancer, College of Medicine and Public Health, Flinders University, Adelaide, Australia.
Ther Adv Med Oncol. 2018 Feb 5;10:1758834018755090. doi: 10.1177/1758834018755090. eCollection 2018.
There is inconsistency in the criteria used to define anti-vascular endothelial growth factor (VEGF) drug-induced hypertension (AVEGF-HT) in published studies. It is unknown whether specific patient characteristics similarly predict AVEGF-HT using different criteria.
We assessed the associations between clinical and demographic factors ( = 22) and AVEGF-HT, using six criteria based on predefined on-treatment blood pressure (BP) thresholds or absolute BP elevations baseline, in a analysis of a phase III trial of 1102 patients with renal cell carcinoma (RCC) randomized to pazopanib or sunitinib (COMPARZ study).
The cumulative incidence of AVEGF-HT at any time while on treatment ranged between 14.8% [criterion: grade ⩾3 toxicity, National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0] and 58.8% (criterion: absolute systolic BP increase ⩾20 mmHg baseline). After adjusting for anti-VEGF treatment and baseline BP, the number of significant ( < 0.05) predictors ranged between one (criterion: absolute systolic BP increase ⩾20 mmHg, on-treatment systolic BP ⩾140 mmHg and diastolic BP ⩾90 mmHg) and nine (criterion: grade ⩾3 toxicity, NCI CTCAE v3.0). Age, use of antidiabetic drugs and use of antihypertensive drugs each significantly predicted four AVEGF-HT criteria. By contrast, sex, smoking, heart rate, proteinuria, Karnofsky performance status, and use of thiazide diuretics did not predict any criterion.
There was a significant variability in the incidence, number and type of predictors of AVEGF-HT, using six different criteria, in a analysis of the COMPARZ study. The use of specific criteria might affect the assessment of the interaction between anti-VEGF drugs, AVEGF-HT and cancer outcomes.
已发表研究中用于定义抗血管内皮生长因子（VEGF）药物所致高血压（AVEGF-HT）的标准存在不一致性。尚不清楚使用不同标准时，特定患者特征是否同样能预测AVEGF-HT。
在一项对1102例肾细胞癌（RCC）患者进行的III期试验（COMPARZ研究）的荟萃分析中，我们基于预先定义的治疗期血压（BP）阈值或相对于基线的绝对BP升高，使用六种标准评估了临床和人口统计学因素（n = 22）与AVEGF-HT之间的关联。这些患者被随机分配接受帕唑帕尼或舒尼替尼治疗。
治疗期间任何时间的AVEGF-HT累积发生率在14.8%[标准：≥3级毒性，美国国立癌症研究所不良事件通用术语标准（NCI CTCAE）v3.0]至58.8%（标准：收缩压绝对升高≥20 mmHg相对于基线）之间。在调整抗VEGF治疗和基线BP后，显著（P < 0.05）预测因素的数量在1个（标准：收缩压绝对升高≥20 mmHg，治疗期收缩压≥140 mmHg且舒张压≥90 mmHg）至9个（标准：≥3级毒性，NCI CTCAE v3.0）之间。年龄、使用抗糖尿病药物和使用抗高血压药物各自显著预测了四种AVEGF-HT标准。相比之下，性别、吸烟、心率、蛋白尿、卡诺夫斯基体能状态以及使用噻嗪类利尿剂均不能预测任何标准。
在COMPARZ研究的荟萃分析中，使用六种不同标准时，AVEGF-HT的发生率、预测因素的数量和类型存在显著差异。使用特定标准可能会影响对抗VEGF药物、AVEGF-HT和癌症结局之间相互作用的评估。
