EVALUATION OF A 24-HOUR INFUSION OF ETIDRONATE DISODIUM FOR THE TREATMENT OF HYPERCALCEMIA OF MALIGNANCY

Background. Hypercalcemia is a serious and common complication of mali gnancy. Etidronate, a known inhibitor of osteoclastic bone resorption, is approved in the therapy of hypercalcemia of malignancy (HCM) at a dose of 7.5 mg/kg/day infused during a period of 2-4 hours on 3 consec utive days. A multicenter study was conducted to evaluate the safety a nd efficacy of a single 24-hour infusion of etidronate disodium in pat ients with HCM. Methods. Selected patients with HCM had disease refrac tory to at least 24-hours of intravenous fluid (more than 3 1/day) wit h two albumin-adjusted serum calcium concentrations greater than 11.5 mg/dl drawn 24 hours apart before etidronate treatment. Thirty patient s were enrolled; 13 received 25 mg/kg for 24 hours, 12 received 30 mg/ kg for 24-hours, 3 received incorrect doses (2 overdoses, and 1 underd ose) and 2 died of disease-related complications before day 7. Of the 25 evaluable patients, 15 were men and 10 were women. Median age was 5 3 years (range, 20-75 years). Twelve patients (6 in each treatment gro up) had confirmed skeletal metastases. Results. During the week after treatment, the 25 mg/ kg group had adjusted serum calcium levels fall from a mean preinfusion baseline of 13.3 +/- 0.3 mg/dl (plus or minus the standard error of the mean) to a mean nadir of 10.9 +/- 0.4 mg/dl (the average of each patient's lowest calcium values). The 30 mg/kg gr oup had adjusted serum calcium levels fall from a mean preinfusion bas eline of 13.8 +/- 0.4 mg/dl to a mean nadir of 10.5 +/- 0.3 mg/dl. The average day that nadir occurred was day 5.7 for the 25 mg/kg group an d day 5.6 for the 30 mg/kg group. The mean maximum reduction (delta) d erived from the patients' nadirs in the 25 mg/kg dose group was 2.5 +/ - 0.4 mg/dl and 3.3 +/- 0.3 mg/dl for the 30 mg/kg dose. Time to effec t (either a partial response defined as a 15% or greater decrease in t he adjusted serum calcium from the preinfusion value or a complete euc alcemic response defined as a reduction to the laboratory's eucalcemic range) occurred on average on day 4.6 in the 25 mg/kg group and day 3 .7 in the 30 mg/kg group. Nine of the 13 (69%) patients in the 25 mg/k g treatment group had either partial or complete response to the 24-ho ur infusion. Five of these patients (38% of the 13 patients) of the 25 mg/kg group had serum calcium levels fall to their laboratory's eucal cemic range before day 7 (a complete response), 4 (31%) had partial re sponse only, and 4 had no response. In the 30 mg/kg group, 11 of 12 (9 2%) patients had at least partial responses. Eight of the 12 (67%) pat ients had adjusted serum calcium concentrations fall to the eucalcemic range by day 7, 3 (25%) had a partial response, and 1 had no response . Reported adverse experiences generally were attributable to the unde rlying disease. The reduction in the serum calcium throughout the week for the 30 mg/kg dose group was significantly greater than that for t he 25 mg/kg group (analysis of variance, P < 0.0001). Conclusions. Eti dronate, when administered intravenously at 30 mg/kg during a period o f 24 hours, apparently was safe and effective in this study for treatm ent of hypercalcemia in patients with a wide variety of tumor types. T his regimen may offer a more convenient method of administration than does standard etidronate therapy for the treatment of HCM.