We thank Ms. Marsha Richardson for assistance with regulatory matters and Mr. Chong Pak for assistance with budgetary matters.
Tolvaptan in hospitalized cancer patients with hyponatremia: A double-blind, randomized, placebo-controlled clinical trial on efficacy and safety
Article first published online: 5 NOV 2013
© 2013 American Cancer Society
Volume 120, Issue 5, pages 744–751, 1 March 2014
How to Cite
Salahudeen, A. K., Ali, N., George, M., Lahoti, A. and Palla, S. (2014), Tolvaptan in hospitalized cancer patients with hyponatremia: A double-blind, randomized, placebo-controlled clinical trial on efficacy and safety. Cancer, 120: 744–751. doi: 10.1002/cncr.28468
- Issue published online: 19 FEB 2014
- Article first published online: 5 NOV 2013
- Manuscript Accepted: 2 OCT 2013
- Manuscript Revised: 1 OCT 2013
- Manuscript Received: 30 JUL 2013
- randomized controlled trial;
- V2-receptor antagonists;
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.
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.
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.
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. Cancer 2014;120:744–751. © 2013 American Cancer Society.