Tolvaptan in hospitalized cancer patients with hyponatremia: a double-blind, randomized, placebo-controlled clinical trial on efficacy and safety.

Background: The rate of hyponatremia is higher in hospitalized cancer patients than in hospitalized patients without cancer and is associated with poor clinical outcomes. The availability of V2 receptor antagonists has been a major breakthrough in the management of hyponatremia, but its efficacy and safety in treating hyponatremia in patients with cancer is not known.

Methods: Adult patients with cancer who were admitted to The University of Texas MD Anderson Cancer Center with nonhypovolemic hyponatremia (125-130 mmol/L) were randomized to receive either tolvaptan or placebo in a double-blind, placebo-controlled, adaptive, randomized trial. Both groups received the standard of care for hyponatremia, except that patients were allowed to drink to thirst.

Results: A preplanned Data Safety Monitoring Board analysis of 30 of 48 randomized patients who completed the study revealed that the primary endpoint of hyponatremia correction was met by 16 of 17 patients who received tolvaptan and by 1 of 13 patients who received placebo (94% vs 8%; P < .001), which met the study stopping rule for superiority. The secondary endpoints between the tolvaptan and placebo groups (mean ± standard deviation) for length of stay (21 ± 15 days vs 26 ± 15 days, respectively) and change in the Mini-Mental State Examination score (-0.35 ± 1.66 vs 0.31 ± 2.42, respectively) were not significantly different. No overcorrection of serum sodium (>12 mmol/L per day) was noted in the tolvaptan group, and the main adverse events noted were dry mouth, polydipsia, and polyuria, leading to 13% study withdrawal.

Conclusions: Although tolvaptan was effective for correcting hyponatremia in patients with cancer, studies with a larger sample size will be required to confirm the current findings, including the outcomes of secondary endpoints.