What is the treatment approach for cancer patients with Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)?

From the Guidelines

The treatment of SIADH in cancer patients should prioritize fluid restriction and addressing the underlying malignancy, with pharmacological options such as vasopressin receptor antagonists and demeclocycline considered for moderate to severe cases, as recommended by the most recent guidelines 1. The management of SIADH in cancer patients involves a multifaceted approach, including:

• Fluid restriction to 800-1000 mL/day to limit free water intake and correct hyponatremia
• Treating the underlying tumor with appropriate chemotherapy, radiation, or surgery to potentially resolve the syndrome
• Pharmacological options, such as:

• Oral salt tablets (3-9 g/day) to enhance free water excretion
• Loop diuretics like furosemide (20-40 mg once or twice daily) to increase sodium levels
• Vasopressin receptor antagonists (vaptans) like tolvaptan (starting at 15 mg daily, adjustable to 30-60 mg) for moderate to severe or symptomatic hyponatremia
• Demeclocycline (300-600 mg twice daily) for chronic management by inducing nephrogenic diabetes insipidus

• In acute, severe cases with neurological symptoms, 3% hypertonic saline may be administered intravenously (typically at 1-2 mL/kg/hour) with close monitoring to avoid rapid correction, which can cause osmotic demyelination syndrome, as noted in recent guidelines 1. It is essential to consider the patient's prognosis and goals of care when managing SIADH, as strict fluid restriction may not be appropriate for patients with a short prognosis, as recommended by recent guidelines 1. The most recent and highest quality study 1 provides the basis for these recommendations, emphasizing the importance of addressing both the underlying malignancy and managing hyponatremia to improve patient outcomes.

From the FDA Drug Label

Tolvaptan tablets are indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia (serum sodium <125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction), including patients with heart failure and Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

The treatment approach for cancer patients with Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) is to use tolvaptan to increase serum sodium levels.

• The usual starting dose for tolvaptan tablets is 15 mg administered once daily without regard to meals.
• The dose can be increased to 30 mg once daily, after at least 24 hours, to a maximum of 60 mg once daily, as needed to achieve the desired level of serum sodium.
• Patients should be in a hospital for initiation and re-initiation of therapy to evaluate the therapeutic response and because too rapid correction of hyponatremia can cause osmotic demyelination resulting in serious neurologic sequelae 2.
• Tolvaptan has been shown to be effective in treating hyponatremia in patients with SIADH, with a statistically significant increase in serum sodium levels compared to placebo 2.

From the Research

Treatment Approach for Cancer Patients with SIADH

The treatment approach for cancer patients with Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) involves several options, including:

• Hypertonic saline infusion for acute presentation 3
• Fluid restriction for chronic asymptomatic evolution 3
• Vaptans, vasopressin receptor antagonists, targeted specifically for the correction of euvolemic hyponatremia 3
• Tolvaptan, an oral selective vasopressin V2-receptor antagonist, which has been shown to be effective and safe in treating hyponatremia in cancer patients with SIADH 4, 5, 6

Tolvaptan as a Treatment Option

Tolvaptan has been studied in several clinical trials and has been shown to be effective in treating hyponatremia in cancer patients with SIADH. The studies have demonstrated that tolvaptan:

• Increases serum sodium levels in a significant proportion of patients 4
• Is safe and well-tolerated, with common treatment-emergent adverse events consistent with previously reported results 4
• Can be initiated in hospital day care units, avoiding the need for hospitalization and improving quality of life 5
• May improve hyponatremia and enable the continued administration of effective chemotherapy in patients with chemotherapy-induced tumour lysis 6

Importance of Proper Diagnosis and Therapy

Proper diagnosis and therapy of cancer-associated hyponatremia are critical to ensure improved outcomes. Understanding the underlying cause of hyponatremia, whether it be SIADH or volume depletion, is essential to provide appropriate treatment 7. The development of targeted therapies, such as vasopressin type 2 receptor antagonists, has offered effective treatment options for patients with SIADH 7.