Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2016 May 11;11(5):e0152079.
doi: 10.1371/journal.pone.0152079. eCollection 2016.

Risk of Hyponatraemia in Cancer Patients Treated with Targeted Therapies: A Systematic Review and Meta-Analysis of Clinical Trials

Rossana Berardi  1 , Matteo Santoni  1 , Silvia Rinaldi  1 , Emilia Nunzi  2 , Alessia Smerilli  3 , Miriam Caramanti  1 , Francesca Morgese  1 , Mariangela Torniai  1 , Agnese Savini  1 , Ilaria Fiordoliva  1 , Azzurra Onofri  1 , Mirco Pistelli  1 , Augusto Taccaliti  3 , Stefano Cascinu  1
Affiliations
Meta-Analysis

Risk of Hyponatraemia in Cancer Patients Treated with Targeted Therapies: A Systematic Review and Meta-Analysis of Clinical Trials

Rossana Berardi et al. PLoS One. .

Abstract

Background: Hyponatraemia has been reported with targeted therapies in cancer patients. Aim of the study was to perform an up-to-date meta-analysis in order to determine the incidence and relative risk (RR) in cancer patients treated with these agents.

Materials and methods: The scientific literature regarding hyponatraemia was extensively reviewed using MEDLINE, PubMed, Embase and Cochrane databases. Eligible studies were selected according to PRISMA statement. Summary incidence, RR, and 95% Confidence Intervals were calculated using random-effects or fixed-effects models based on the heterogeneity of selected studies.

Results: 4803 potentially relevant trials were identified: of them, 13 randomized phase III studies were included in this meta-analysis. 6670 patients treated with 8 targeted agents were included: 2574 patients had hepatocellular carcinoma, whilst 4096 had other malignancies. The highest incidences of all-grade hyponatraemia were observed with the combination of brivanib and cetuximab (63.4) and pazopanib (31.7), while the lowest incidence was reported by afatinib (1.7). The highest incidence of high-grade hyponatraemia was reported by cetuximab (34.8), while the lowest incidences were reported by gefitinib (1.0). Summary RR of developing all-grade and high-grade hyponatraemia with targeted agents was 1.36 and 1.52, respectively. The highest RRs of all-grade and high-grade hyponatraemia were associated with brivanib (6.5 and 5.2, respectively). Grouping by drug category, the RR of high-grade hyponatraemia with angiogenesis inhibitors was 2.69 compared to anti-Epidermal Growth Factor Receptors agents (1.12).

Conclusion: Treatment with biological therapy in cancer patients is associated with a significant increased risk of hyponatraemia, therefore frequent clinical monitoring should be emphasized when managing targeted agents.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: Rossana Berardi received consulting fee or honoraria from Otsuka, Lilly, Italfarmaco; Stefano Cascinu received consulting fee or honoraria from Lilly, Amgen, Roche and they have received a research funding (paid to their Institution) from BMS for a research project. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. The other authors declare that they have no competing interests.

Figures

Fig 1
Fig 1. Selection of randomized controlled trials included in the meta-analysis according to PRISMA statement.
Fig 2
Fig 2. Relative Risk (RR) of all-grade hyponatraemia associated with targeted therapy by individual study.
Fig 3
Fig 3. Relative Risk of high-grade hyponatraemia associated with targeted therapy by individual study.
Fig 4
Fig 4. Relative Risk of high-grade hyponatraemia by drug category.
See this image and copyright information in PMC

References

    1. Castillo JJ, Vincent M, Justice E. Diagnosis and management of hyponatraemia in cancer patients. The Oncologist 2012;17:756–765 10.1634/theoncologist.2011-0400 - DOI - PMC - PubMed
    1. Doshi SM, Shah P, Lei X, et al. Hyponatraemia in hospitalized cancer patients and its impact on clinical outcomes. Am J Kidney Dis 2012;59:222–228. 10.1053/j.ajkd.2011.08.029 - DOI - PubMed
    1. Schutz FA, Xie W, Donskov F, Sircar M, McDermott DF, Rini BI et al. The impact of low serum sodium on treatment outcome of targeted therapy in metastatic renal cell carcinoma: results from the International Metastatic Renal Cell Cancer Database Consortium. Eur Urol 2014;65:723–730. 10.1016/j.eururo.2013.10.013 - DOI - PMC - PubMed
    1. Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg 2010;8:336–431. 10.1016/j.ijsu.2010.02.007 - DOI - PubMed
    1. Je Y, Schutz FA, Choueiri TK. Risk of bleeding with vascular endothelial growth factor receptor tyrosine-kinase inhibitors sunitinib and sorafenib: a systematic review and meta-analysis of clinical trials. Lancet Oncol 2009;10:967–974. 10.1016/S1470-2045(09)70222-0 - DOI - PubMed

LinkOut - more resources