Jeannette Y. Wick, RPh, MBA, FASCP
The vasopressin-2 receptor antagonist tolvaptan was effective at treating hyponatremia in 10 patients with small cell lung cancer, according to a prospective case series report.
Highly malignant small cell lung cancer (SCLC) tumors are often associated with paracrine and paraneoplastic syndromes. Ten to 15% of patients with SCLC develop hyponatremia (plasma sodium < 125 mmol/L), a problem that has befuddled clinicians since its recognition in 1957. One cause of hyponatremia, syndrome of inappropriate antidiuretic hormone secretion (SIADH), usually presents in advanced stages with dizziness, tremor, agitation, and other neuropsychiatric symptoms, especially fatigue.
In SCLC patients, hyponatremia is associated with a high morbidity and mortality. Its severity can be so significant that it forces patients to delay cancer treatment. Correcting the sodium deficiency is critical so chemotherapy can be started or resumed. Conventional options (eg, fluid restriction, sodium chloride supplementation, and demeclocycline) have often failed to help. Failure to correct the problem contributes to poorer prognoses.
A team of researchers from the Evangelische Lungenklinik Berlin in Germany, acknowledging that hyponatremia has been very difficult to manage in SCLC patients, has investigated vasopressin-2 receptor antagonists as treatment options. In an article
published in the August 2013 issue of BMC Pulmonary Medicine
, the researchers present a prospective case series using tolvaptan in 10 patients.
The researchers selected their cases based on a histologically confirmed SCLC diagnosis and clinical observation of a neurocognitive deficit caused by SIADH-related hyponatremia. They developed and used a treatment algorithm that they followed with every patient in an inpatient setting. Their monitoring included ECOG performance status, commencement of chemotherapy, and correction of sodium levels.
The researchers employed a tolvaptan dose of 15 mg per day. All patients’ plasma sodium levels improved significantly, with a median of 4 days of treatment per episode of hyponatremia. Only 2 patients needed treatment for longer than 10 days. Patients’ plasma sodium remained in the normal range for a median of 17.5 days (range 2 to 614 days), allowing all patients to start or resume chemotherapy. ECOG performance status improved, and prolonged hospital stays were avoided. The researchers observed no serious events related to tolvaptan. Of note, the median age in this cohort was 70 years, and when the paper went to press 2 patients were still alive, having survived longer than 20 months.
Based on these results, adopting new approaches to management of SIADH in thoracic oncology may improve outcomes and allow patients to start or resume chemotherapy promptly.
Ms. Wick is a visiting professor at the University of Connecticut School of Pharmacy and a freelance writer from Virginia.