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 malignancy. 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 consecutive days. A multicenter study was conducted to evaluate the safety and efficacy of a single 24‐hour infusion of etidronate disodium in patients with HCM. Methods. Selected patients with HCM had disease refractory to at least 24‐hours of intravenous fluid (more than 3 I/day) with two albumin‐adjusted serum calcium concentrations greater than 11.5 mg/dl drawn 24 hours apart before etidronate treatment. Thirty patients 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 underdose) 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 53 years (range, 20–75 years). Twelve patients (6 in each treatment group) 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 group had adjusted serum calcium levels fall from a mean preinfusion baseline 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 and day 5.6 for the 30 mg/kg group. The mean maximum reduction (delta) derived 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 effect (either a partial response defined as a 15% or greater decrease in the adjusted serum calcium from the preinfusion value or a complete eucalcemic 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/kg treatment group had either partial or complete response to the 24‐hour 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 eucalcemic range before day 7 (a complete response), 4 (31%) had partial response only, and 4 had no response. In the 30 mg/kg group, 11 of 12 (92%) patients had at least partial responses. Eight of the 12 (67%) patients 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 underlying disease. The reduction in the serum calcium throughout the week for the 30 mg/kg dose group was significantly greater than that for the 25 mg/kg group (analysis of variance, P < 0.0001). Conclusions. Etidronate, when administered intravenously at 30 mg/kg during a period of 24 hours, apparently was safe and effective in this study for treatment of hypercalcemia in patients with a wide variety of tumor types. This regimen may offer a more convenient method of administration than does standard etidronate therapy for the treatment of HCM. Cancer 1994; 73:2527—34.