Increased bleeding risk associated with concurrent vascular endothelial growth factor receptor tyrosine kinase inhibitors and low-molecular-weight heparin

被引：15

作者：

Patel, Sandip H. ^{[1
,2
]}

George, Tiffany L. ^{[1
,2
]}

Wang, Tzu-Fei ^{[2
,3
,4
]}

Vogt, Sherry M. ^{[5
,6
]}

Folefac, Edmund ^{[1
]}

Xu, Menglin ^{[1
]}

Yang, Yuanquan ^{[1
]}

Parikh, Anish B. ^{[1
]}

Verschraegen, Claire F. ^{[1
]}

Clinton, Steven K. ^{[1
]}

Yin, Ming ^{[1
]}

机构：

[1] Ohio State Univ, Coll Med, Dept Internal Med, Div Med Oncol, 370 W 9th Ave, Columbus, OH 43210 USA

[2] Ohio State Univ, Coll Med, Dept Internal Med, Div Hematol, Columbus, OH 43210 USA

[3] Univ Ottawa, Ottawa Hosp, Dept Med, Ottawa, ON, Canada

[4] Ottawa Hosp, Res Inst, Ottawa, ON, Canada

[5] Ohio State Univ, Dept Pharm, James Canc Hosp, Columbus, OH 43210 USA

[6] Richard J Solove Res Inst, Columbus, OH USA

来源：

CANCER | 2021年 / 127卷 / 06期

关键词：

bleeding; cancer; direct oral anticoagulant (DOAC); factor Xa inhibitor; low‐ molecular‐ weight heparin (LMWH); tyrosine kinase inhibitor; vascular endothelial growth factor receptor (VEGFR); RENAL-CELL CARCINOMA; VENOUS THROMBOEMBOLISM; SUNITINIB; THERAPY; CANCER; ANGIOGENESIS; DEFINITION; PATHWAY; EVENTS; VEGFR;

D O I：

10.1002/cncr.33337

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background Some cancer patients who are diagnosed with thromboembolism may require dual treatment with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) and factor Xa inhibitors (low-molecular-weight heparin [LMWH] or direct oral anticoagulants [DOACs]). However, to the authors' knowledge, the safety of such combinations has not been well characterized. Methods Patients with advanced cancer who were treated with concurrent VEGFR TKIs and factor Xa inhibitors between 2010 and 2018 at The Ohio State University Comprehensive Cancer Center were included. Charts were reviewed retrospectively for clinically significant bleeding events occurring during concurrent treatment compared with those occurring during factor Xa inhibitor therapy alone, using each patient as their own control. The Fisher exact test was used to compare distribution of bleeding severities. The Cox proportional hazards model was used to compare bleeding risk between groups. Results Among 86 patients, there were 29 clinically significant bleeding events (including 8 major bleeding events) reported during concurrent treatment and 17 events (including 4 major bleeding events) reported during factor Xa inhibitor therapy alone over a median follow-up of 63 days. Concurrent treatment was associated with significantly higher risks of overall bleeding (hazard ratio, 2.45; 95% confidence interval, 1.28-4.69 [P = .007]) and first-onset bleeding (hazard ratio, 2.23; 95% confidence interval, 1.13-4.42 [P = .02]). Analysis of 6-month bleeding risk and the subgroups of patients treated with concurrent TKIs and LMWH versus LMWH alone demonstrated a similar trend. The sample size was inadequate for comparisons between treatment with concurrent TKIs and DOACs versus DOACs alone. Conclusions Concurrent treatment with VEGFR TKIs and LMWH was found to be associated with a significantly increased risk of bleeding events when compared with LMWH therapy alone.

引用

页码：938 / 945

页数：8