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

• Published in: PloS one Vol. 11; no. 5; p. e0152079
• Main Authors: Berardi, Rossana, Santoni, Matteo, Rinaldi, Silvia, Nunzi, Emilia, Smerilli, Alessia, Caramanti, Miriam, Morgese, Francesca, Torniai, Mariangela, Savini, Agnese, Fiordoliva, Ilaria, Onofri, Azzurra, Pistelli, Mirco, Taccaliti, Augusto, Cascinu, Stefano
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11.05.2016; Public Library of Science (PLoS)
• Subjects: Angiogenesis inhibitors; Biology and Life Sciences; Cancer; Cancer patients; Cancer therapies; Cancer treatment; Care and treatment; Chemotherapy; Clinical trials; Clinical Trials, Phase III as Topic; Complications and side effects; Confidence intervals; Demographic aspects; Endocrinology; Epidermal growth factor; Epidermal growth factor receptors; Gefitinib; Growth factor receptors; Health risks; Hepatocellular carcinoma; Humans; Hyponatremia; Hyponatremia - complications; Incidence; Kidney cancer; Liver cancer; Lung cancer; Medical prognosis; Medical research; Medicine and Health Sciences; Meta-analysis; Metastasis; Monoclonal antibodies; Neoplasms - complications; Patient outcomes; Patients; Physical Sciences; Randomized Controlled Trials as Topic; Receptors; Research and Analysis Methods; Risk; Risk Factors; Risk management; Studies; Systematic review; Targeted cancer therapy; Tumors; Italy
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0152079

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. 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. 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). 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.