Treatment of tumor hypercalcemia with clodronate

In an open, controlled study 34 patients with tumor hypercalcemia of different origin were treated with clodronate. The initial dosage was 300 mg intravenously daily. After achieving normocalcemia, treatment was continued orally using 400-3200 mg/day depending on serum calcium concentration. Most patients showed normocalcemia within 1 week of treatment - only few of them needed a longer time. Fifteen of 34 patients died within the observation time of up to 24 weeks, some being normocalcemic. However, a reincrease in plasma calcium during treatment was an indicator of deterioration. Measurements of plasma parathyroid hormone (PTH) using an intact molecule radioimmunometric assay showed depressed levels before clodronate treatment started, but PTH rose after achieving normal and especially low normal calcium levels. Starting 1,25-dihydroxycholecalciferol [1,25(OH)2D3] values were decreased or in the lower normal range in the majority of patients, but in 6/21 patients plasma 1,25(OH)2D3 was in the upper normal range or elevated despite hypercalcemia. After lowering plasma calcium the 1,25(OH)2D3 levels increased. However, there was no significant correlation between PTH and 1,25(OH)2D3. Therefore we assume that in some patients additional stimulation of renal 1 alpha-hydroxylase by tumor products is present.