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Page 10 of 12 Khan et al. J Cancer Metastasis Treat 2019;5:71 I http://dx.doi.org/10.20517/2394-4722.2019.017

As compared with fluid restriction, lithium and urea, vaptans offer a therapeutic option that is patho-
[41]
physiologically focused, potent and effective . Despite efficacy of vaptans in improving serum sodium,
clinical practice guideline on the diagnosis and treatment of hyponatremia do not recommend the use of
[23]
vaptans due to concern for overcorrection of sodium and lack of mortality benefit . The safety and efficacy
of tolvaptan was evaluated in a post hoc subgroup analysis of the patients with cancer in SALT-1 (study of
ascending levels of tolvaptan in hyponatremia) and SALT-2 clinical trials. Baseline sodium in the cohort
of the SALT trials was 130 mEq/L. A 15 mg dose of tolvaptan was titrated up to 30 or 60 mg over 4 days
if the increase in serum sodium was < 5 mEq/L in the prior 24 h. Tolvaptan was withheld or reduced and
fluid intake was increased if serum sodium was > 145 mEq/L. Serum sodium normalized to > 135 mEq/L
in 66.6% of the patients by day 30. Serum sodium exceeded the desired rate of correction (> 8 mEq/L over
the first 8 h of therapy or > 12 mEq/L over 24 h) in 1.8% of patients. None of these patients developed any
[6]
symptoms of osmotic demyelination syndrome .
In our experience, vaptans are well tolerated by cancer patients and offer a therapeutic option in patients
with euvolemic and hypervolemic hyponatremia when fluid restriction alone is insufficient to increase
serum sodium levels or to avoid the discomfort associated with fluid restriction. Although the vaptans
are well tolerated and effective, their high cost continues to be a limitation for routine use. In a post hoc
analysis, economic models from SALT-1, SALT-2 and EVERST reported decrease in length of stay in
[44]
the hospital and hospital cost savings with tolvaptan use . To reduce the risk of hyponatremia all i.v.
medications should be concentrated and hypotonic i.v. fluids should be avoided in hospitalized patients,
[45]
e.g., perioperatively, during cancer chemotherapy, bronchitis, pneumonia or lung disease .

CONCLUSION
Oncology patients with hyponatremia need close monitoring of fluid intake and output to prevent
derangements in salt and volume balance. Hyponatremia in cancer patients is associated with advanced
[9]
disease and poor prognosis. Improvement in serum sodium correlates with improved survival . Whether
the treatment of hyponatremia improves overall survival needs to be investigated. Proposed algorithms for
the management of hyponatremia could be utilized in patients with cancer, recognizing that hyponatremia
is of diverse etiology in this population. Use of therapeutic agents such as the vaptans offer a convenient,
effective, and targeted approach to the management of hyponatremia. Further studies are likely to clarify
cost effectiveness and safety concerns related to vaptan use in cancer patients.

DECLARATIONS
Authors’ contributions
Wrote the first draft of the manuscript: Khan MI
Provided critical edits to the manuscript: Waguespack SG, Ahmed I
Approved the final version of the manuscript: Khan MI, Waguespack SG, Ahmed I

Availability of data and materials
Not applicable.

Financial support and sponsorship
Not applicable.

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.