Hyperphosphataemia in dialysis patients with end-stage renal disease (ESRD) is an important contributor to morbidity and mortality; therefore, effective phosphate binders are needed to reduce serum phosphate levels.

An extensive programme of clinical trials has established schedules for effective management of hyperphosphataemia in ESRD patients using lanthanum carbonate.

Three placebo-controlled, double-blind, randomized trials of similar design have been carried out to assess efficacy of lanthanum carbonate in ESRD patients in the USA, Taiwan and Europe.^1-3  In all three studies, serum phosphate was significantly lower in the lanthanum group than in the placebo group, by study endpoint, showing similar efficacy in different populations.
Patient compliance was good in all three studies (mean compliance over the double-blind period: USA 87%; Europe 91%; Taiwan 95%).

Two large-scale trials have investigated long-term control of hyperphosphataemia in ESRD by randomizing patients to lanthanum carbonate or alternative treatment. In study SPD405-301, lanthanum carbonate was compared with calcium carbonate was compared with calcium carbonate (CC) during a 6-month period.⁴ During the 5-week titration period, in which lanthanum carbonate was raised to optimal levels and patients were therefore more likely to have received an effective dose in the CC arm, serum phosphate control was better in the CC-treated (P=0.002). By Week 25, 66% of patients who received lanthanum carbonate had achieved serum phosphate control. Lanthanum carbonate improved hyperphosphataemia without elevating calcium levels; this was in contrast to the CC-treated group, in which hypercalcaemia was reported in 20% of patients. In Study SPD405-307, lanthanum carbonate was compared with standard, primarily calcium-based, treatments.⁵ In this 2-year study, 1359 patients were randomized 1:1 to receive lanthanum carbonate (n=682) or their pre-study conventional phosphate binder (n=677).  During the treatment period, which was completed by 517 patients (38%), lanthanum carbonate showed similar efficacy to standard treatment.

In conclusion, the minimum effective dose is 750 mg, and 1500-3000 mg of lanthanum carbonate reduces serum phosphate levels to clinically desirable levels in the majority of patients, irrespective of ethnic group and without raising calcium levels. Lanthanum carbonate, therefore, provides a potent treatment option and a more precise tool for hyperphosphataemia control than calcium-based agents.

References:

1. Hutchison AJ, Speake M, Al Baaj F.  Reducing high phosphate levels in patients with chronic renal failure undergoing dialysis: a 4-week, dose-finding, open-label study with lanthanum carbonate.  Nephrol Dial Transplant 2004; 19:1902-6

2. Joy MS, Finn WF.  Randomized, double-blind, placebo-controlled, dose-titration, Phase III study assessing the efficacy and tolerability of lanthanum carbonate: a new phosphate binder for the treatment of hyperphosphatemia.  Am J Kidney Dis 2003;42:96-107

3. Yang WC, Chaing SS, Chen JB.  Efficacy and safety of lanthanum carbonate in the treatment of hyperphosphatemia in Chinese chronic renal failure patients.  Poster presented at the 36^th Annual Meeting of the American Society of Nephrology, San Diego, CA, USA, 12-17 November 2003

4. Hutchison AJ, Maes B, Vanwalleghem J et al.  Efficacy, tolerability, and safety of lanthanum carbonate in hyperphosphatemia: a 6-month, randomized, comparative trial versus calcium carbonate.  Nephron Clin Pract 2005; 100 c8-19

5.Finn WF, Joy MS, Webster I.  Lanthanum carbonate (Fosrenol^®) versus standard therapy in hyperphosphatemia: interim findings from a 2-year safety and outcomes study.  Poster presented at the 36^th Annual Meeting of the American Society of Nephrology, San Diego, CA, USA, 17-17 November 2003