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

Abstract

BackgroundHyponatraemia 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 MethodsThe 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.Results4803 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).ConclusionTreatment 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.

Copeptin is not useful as a marker of malignant disease in the syndrome of inappropriate antidiuresis

“…Of note, cancer patients are often polymedicated (e.g. chemotherapy such as vincristine and cisplatin, pain killers) or in an unstable condition and may, therefore, be particularly prone to hyponatremia (30). Third, irrespective of SIAD, copeptin is known to be elevated due to stress and acute conditions such as pneumonia, stroke or heart failure (31,32,33).…”

Managing hyponatremia in lung cancer: latest evidence and clinical implications

“… 5 Few studies have specifically focused on non-small cell lung cancer (NSCLC) patients. 2 , 9 – 12 The estimated incidence of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in this subgroup of patients is about 2–4%. 9 …”

The management of hyponatremia in cancer patients: a practical view in Spain

“…When SIADH-induced hyponatremia is caused by the anti-cancer treatment itself (for example, vincristine) [8] , a modification of cancer therapy should be considered. When a change in medication is not feasible, SIADH in these cases should be treated with Tolvaptan.…”

“…Hyponatremia can also be attributed to other etiologies that are not related per se to the cancer. What is more, hyponatremia can be induced by cancer-related complications, as well as the anti-cancer treatment itself [8] or the side effects of cancer therapy. These include diarrhea, nausea, vomiting, pain, nephrotoxicity, adrenal insufficiency (due to adrenal metastases), etc.…”