Incidence and risk of hypertension with pazopanib in patients with cancer: a meta-analysis

Cancer Chemother Pharmacol. 2013 Feb;71(2):431-9. doi: 10.1007/s00280-012-2025-5. Epub 2012 Nov 21.

Abstract

Purposes: To gain a better understanding of the overall incidence and risk of hypertension in cancer patients who receive pazopanib and to compare the differences in incidence among sorafenib, sunitinib, and pazopanib.

Methods: Several databases were searched, including PubMed, Embase, and Cochrane databases. Eligible studies were phase II and III prospective clinical trials of patients with cancer assigned single drug pazopanib 800 mg/day with data on hypertension available. Overall incidence rates, relative risk (RR), and 95 % confidence intervals (CI) were calculated employing fixed or random effects models depending on the heterogeneity of the included trials.

Results: A total of 1,651 patients with a variety of solid tumors from 13 clinical trials were included for the meta-analysis. The overall incidences of all-grade and high-grade hypertension in cancer patients were 35.9 % (95 % CI 31.5-40.6 %) and 6.5 % (95 % CI 5.2-8.0 %), respectively. The use of pazopanib was associated with an increased risk of developing all-grade (RR 4.97, 95 % CI 3.38-7.30, p < 0.001) and high-grade hypertension (RR 2.87, 95 % CI 1.16-7.12, p = 0.023). Additionally, there was no significant difference in the incidence of all-grade (RR 1.21, 95 % CI 0.96-1.53, p = 0.11) and high-grade hypertension (RR 1.29, 95 % CI 0.80-2.07, p = 0.30) between RCC and non-RCC patients. Interestingly, the risk of all-grade hypertension with pazopanib was substantially higher than sorafenib (RR 1.99; 95 % CI 1.73-2.29, p = 0.00) and sunitinib (RR 2.20; 95 % CI 1.92-2.52, p = 0.00), while the risk of pazopanib-induced high-grade hypertension was similar to sorafenib (RR 0.98; 95 % CI 0.75-1.30, p = 0.90) and sunitinib (RR 0.81; 95 % CI 0.62-1.06, p = 0.12).

Conclusions: The use of pazopanib is associated with a significantly increased risk of developing hypertension. Close monitoring and appropriate managements are recommended during the therapy. Future studies are still needed to investigate the risk reduction and possible use of pazopanib in selected patients.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / adverse effects*
  • Clinical Trials as Topic*
  • Humans
  • Hypertension / chemically induced*
  • Hypertension / epidemiology
  • Incidence
  • Indazoles
  • Neoplasms / drug therapy*
  • Prospective Studies
  • Publication Bias
  • Pyrimidines / adverse effects*
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors
  • Risk
  • Sulfonamides / adverse effects*

Substances

  • Angiogenesis Inhibitors
  • Indazoles
  • Pyrimidines
  • Sulfonamides
  • pazopanib
  • Receptors, Vascular Endothelial Growth Factor