Low sodium levels linked to poor targeted therapy outcomes in RCC

Low serum sodium levels in patients receiving targeted therapy for metastatic renal cell carcinoma (mRCC) may signal a poor outcome, study findings indicate.

The results showed that patients with low sodium levels, or hyponatremia, had a 57% increased risk for treatment failure, a 51% increased risk for death, and a 50% reduction in the odds for achieving disease control, compared with patients with normal levels, after taking into account International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk factors.

“Hyponatremia might be a quick and efficient method of stratifying patients beyond the IMDC criteria,” suggest the researchers, led by Toni Choueiri (Harvard Medical School, Boston, Massachusetts, USA).

Of the 1661 patients treated with first-line vascular endothelial growth factor or mammalian target of rapamycin targeted therapy, 243 (14.6%) had hyponatremia, with a baseline serum sodium level below 135 mmol/L.

Overall survival in these patients was significantly shorter at a median of 7.0 months versus 20.9 months for those with normal serum sodium levels.

Similarly, the time to treatment failure was shorter among those with than without hyponatremia (2.9 vs 7.4 months), as was the disease control rate (55 vs 79%).

The patients with hyponatremia tended to have other unfavorable prognostic features, but the negative effect of hyponatremia on treatment outcome remained significant even after adjusting for these features.

Baseline serum sodium level also independently predicted overall survival, time to treatment failure, and disease control rate when it was assessed as a continuous variable.

The researchers calculated that with each 3 mmol/L decrease in serum sodium levels, the risk for death increased by 19%, the risk for treatment failure by 20%, and the odds for achieving disease control decreased by 23%.

They comment in European Urology that patients with baseline hyponatremia are likely to have a more aggressive form of cancer or a poor tolerance to therapy. It therefore remains unknown whether aggressive treatment of hyponatremia will alter the outcome of mRCC patients treated with targeted therapies.

Nevertheless, they believe that hyponatremia “deserves to be further investigated as a prognostic factor and evaluated for inclusion in future prognostic tools.”

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