title: Risk of Hyponatraemia in Cancer Patients Treated with Targeted Therapies: A Systematic Review and Meta-Analysis of Clinical Trials.
abstract: 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.
authors.affiliation: Clinica di Oncologia Medica, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Ancona, Italy.
authors.forename: Rossana
authors.initials: R
authors.lastname: Berardi
authors.affiliation: Clinica di Oncologia Medica, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Ancona, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Santoni
authors.affiliation: Clinica di Oncologia Medica, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Ancona, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Rinaldi
authors.affiliation: Dipartimento Medicina Sperimentale, Università degli Studi di Perugia, Perugia, Italy.
authors.forename: Emilia
authors.initials: E
authors.lastname: Nunzi
authors.affiliation: Division of Endocrinology, A-Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Ancona, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Smerilli
authors.affiliation: Clinica di Oncologia Medica, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Ancona, Italy.
authors.forename: Miriam
authors.initials: M
authors.lastname: Caramanti
authors.affiliation: Clinica di Oncologia Medica, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Ancona, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Morgese
authors.affiliation: Clinica di Oncologia Medica, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Ancona, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Torniai
authors.affiliation: Clinica di Oncologia Medica, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Ancona, Italy.
authors.forename: Agnese
authors.initials: A
authors.lastname: Savini
authors.affiliation: Clinica di Oncologia Medica, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Ancona, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Fiordoliva
authors.affiliation: Clinica di Oncologia Medica, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Ancona, Italy.
authors.forename: Azzurra
authors.initials: A
authors.lastname: Onofri
authors.affiliation: Clinica di Oncologia Medica, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Ancona, Italy.
authors.forename: Mirco
authors.initials: M
authors.lastname: Pistelli
authors.affiliation: Division of Endocrinology, A-Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Ancona, Italy.
authors.forename: Augusto
authors.initials: A
authors.lastname: Taccaliti
authors.affiliation: Clinica di Oncologia Medica, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I-GM Lancisi-G Salesi, Ancona, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Cascinu
mesh_terms: D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D007010:Hyponatremia / Q000150:complications*; D015994:Incidence; D009369:Neoplasms / Q000150:complications*; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors