SINGLE-DOSE INTRAVENOUS THERAPY WITH PAMIDRONATE FOR THE TREATMENT OFHYPERCALCEMIA OF MALIGNANCY - COMPARISON OF 30-MG, 60-MG, AND 90-MG DOSAGES

PURPOSE: To determine the efficacy, dose-response relationship, and sa fety of 30, 60, and 90 mg of a single intravenous dose of an aminobisp hosphonate, pamidronate (APD), for the treatment of moderate to severe hypercalcemia of PATIENTS AND METHODS: Patients with histologically p roven cancer and a corrected serum calcium level of at least 12.0 mg/d L after 48 hours of normal saline hydration were enrolled in a double- blind, multicenter, randomized clinical trial. Pamidronate in 30-, 60- , or 90-mg doses was administered as a single 24-hour infusion. Serum calcium corrected for albumin, urine hydroxyproline, and calcium excre tion, and serum parathyroid hormone (PTH) (1-84) were determined befor e and after pamidronate therapy. RESULTS: Thirty-two men and 18 women entered the study. A dose-response relationship for normalization of c orrected serum calcium was seen after pamidronate administration. Corr ected serum calcium normalized in 40% of patients who received 30 mg, in 61% of patients who received 60 mg, and in 100% of patients who rec eived 90 mg of pamidronate. The decline in the serum calcium level was associated with decreased osteoclastic skeletal resorption evidenced by a decrease in urine calcium and hydroxyproline excretion. Among tho se with a normalization corrected serum calcium level the mean (median ) duration of normalization of the corrected serum calcium value was 9 .2 (4),13.3 (5), and 10.8 (6) days in the 30-, 60-, and 90-mg treatmen t groups, respectively. The response of hypercalcemia to pamidronate w as not significantly influenced by the presence of skeletal metastases . PTH 1-84, suppressed in patients on entry into this study, increased to a greater extent in those patients with osteolytic skeletal metast ases compared with those with humoral hypercalcemia of malignancy. Cli nical improvement, including improved mental status and decreased anor exia, accompanied the decline in the corrected serum calcium level in all three treatment groups. Side effects included low-grade fever, asy mptomatic hypocalcemia, hypomagnesemia, and hypophosphatemia. CONCLUSI ONS: A single-dose infusion of 60 to 90 mg of pamidronate was highly e ffective and well tolerated and normalized corrected serum calcium in nearly all patients (61% to 100%) with hypercalcemia of malignancy.