Neuropathy with vascular endothelial growth factor receptor tyrosine kinase inhibitors: A meta-analysis

Bhaskar Roy; Avash Das; Kumar Ashish; Dhrubajyoti Bandyopadhyay; Abhishek Maiti; Sandipan Chakraborty; Martha E Stone; Lisa Liang Philpotts; Richard J Nowak; Huned S Patwa

doi:10.1212/WNL.0000000000007743

Neuropathy with vascular endothelial growth factor receptor tyrosine kinase inhibitors: A meta-analysis

Neurology. 2019 Jul 9;93(2):e143-e148. doi: 10.1212/WNL.0000000000007743. Epub 2019 Jun 5.

Affiliations

¹ From the Department of Neurology (B.R., R.J.N., H.S.P.), Division of Neuromuscular Medicine, Yale School of Medicine, New Haven, CT; Department of Molecular Genetics (A.D.), University of Texas Southwestern Medical Center, Dallas; Crozer-Chester Medical Center (K.A.), Upland, PA; Division of Internal Medicine (D.B.), St. Luke Roosevelt Medical Center, Mount Sinai, NY; Division of Cancer Medicine (A.M.), the University of Texas MD Anderson Cancer Center, Houston; Department of Internal Medicine (S.C.), Interfaith Medical Center, Brooklyn, NY; and Treadwell Library (M.E.S., L.L.P.), Massachusetts General Hospital, Boston. bhaskar.roy@yale.edu.
² From the Department of Neurology (B.R., R.J.N., H.S.P.), Division of Neuromuscular Medicine, Yale School of Medicine, New Haven, CT; Department of Molecular Genetics (A.D.), University of Texas Southwestern Medical Center, Dallas; Crozer-Chester Medical Center (K.A.), Upland, PA; Division of Internal Medicine (D.B.), St. Luke Roosevelt Medical Center, Mount Sinai, NY; Division of Cancer Medicine (A.M.), the University of Texas MD Anderson Cancer Center, Houston; Department of Internal Medicine (S.C.), Interfaith Medical Center, Brooklyn, NY; and Treadwell Library (M.E.S., L.L.P.), Massachusetts General Hospital, Boston.

PMID: 31167931
DOI: 10.1212/WNL.0000000000007743

Abstract

Objective: To explore the association of peripheral neuropathy with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) use in patients with cancer.

Methods: Published data search up to November 2018 reporting peripheral neuropathy in patients with cancer treated with VEGFR-TKIs was performed. The primary outcome was presence of peripheral neuropathy at the end of the trial. Random-effects meta-analysis was performed to estimate relative risk (RR) of individual treatment.

Results: Thirty randomized clinical trials (RCTs) including 12,490 patients with cancer were included in this analysis. Eight studies compared VEGFR-TKIs with placebo and the remaining studies compared VEGFR-TKIs with the standard chemotherapeutic regimen. When compared against placebo, VEGFR-TKIs were associated with a higher risk of peripheral neuropathy (RR 1.76; 95% confidence interval [CI] 1.13-2.75, p = 0.01). Similarly, a stronger association was noted for sensory neuropathy with VEGFR-TKIs monotherapy (RR 1.61; 95% CI 1.09-2.37, p = 0.02). Risk of peripheral neuropathy with VEGFR-TKIs was higher even when they were compared against control (either placebo or standard chemotherapeutic agents) (RR 1.08; 95% CI 1.01-1.15, p = 0.03). High-grade neuropathy (RR 1.28; 95% CI 1.06-1.54, p <0.01) and high-grade sensory neuropathy (RR 1.38; 95% CI 1.09-1.74, p < 0.01) were noted more frequently with VEGFR-TKIs treatment compared against control.

Conclusions: VEGFR-TKIs therapy appeared to be associated with an increased risk of neuropathy.

Publication types

Meta-Analysis
Systematic Review

MeSH terms

Humans
Neoplasms / drug therapy*
Peripheral Nervous System Diseases / epidemiology*
Protein Kinase Inhibitors / therapeutic use*
Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors*

Substances

Protein Kinase Inhibitors
Receptors, Vascular Endothelial Growth Factor