In a third multicenter, randomized, parallel double-blind trial, a group of 69 cancer patients with hypercalcemia was enrolled to receive 60 mg of Aredia as a 4- or 24-hour infusion, which was compared to a saline-treatment group. Patients who had a corrected serum calcium level of ≥ 12.0 mg/dL after 24 hours of saline hydration were eligible for this trial.

The mean baseline-corrected serum calcium levels for Aredia 60-mg 4-hour infusion, Aredia 60-mg 24-hour infusion, and saline infusion were 14.2 mg/dL, 13.7 mg/dL, and 13.7 mg/dL, respectively.

By Day 7 after initiation of treatment, 78%, 61%, and 22% of the patients had normal- corrected serum calcium levels for the 60-mg 4-hour infusion, 60-mg 24-hour infusion, and saline infusion, respectively. At Day 14, 39% of the patients in the Aredia 60-mg 4-hour infusion group and 26% of the patients in the Aredia 60-mg 24-hour infusion group had normal-corrected serum calcium levels or maintenance of a partial response.

For responders, the median duration of complete responses was 4 days and 6.5 days for Aredia 60-mg 4-hour infusion and Aredia 60-mg 24-hour infusion, respectively.

In all three trials, patients treated with Aredia had similar response rates in the presence or absence of bone metastases. Concomitant administration of furosemide did not affect response rates.

Thirty-two patients who had recurrent or refractory hypercalcemia of malignancy were given a second course of 60 mg of Aredia over a 4- or 24-hour period. Of these, 41% showed a complete response and 16% showed a partial response to the retreatment, and these responders had about a 3-mg/dL fall in mean-corrected serum calcium levels 7 days after retreatment.

In a fourth multicenter, randomized, double-blind trial, 103 patients with cancer and hypercalcemia (corrected serum calcium ≥ 12.0 mg/dL) received 90 mg of Aredia as a 2-hour infusion. The mean baseline corrected serum calcium was 14.0 mg/dL. Patients were not required to receive IV hydration prior to drug administration, but all subjects did receive at least 500 mL of IV saline hydration concomitantly with the pamidronate infusion. By Day 10 after drug infusion, 70% of patients had normal corrected serum calcium levels ( < 10.8 mg/dL).

Paget's Disease

Paget's disease of bone (osteitis deformans) is an idiopathic disease characterized by chronic, focal areas of bone destruction complicated by concurrent excessive bone repair, affecting one or more bones. These changes result in thickened but weakened bones that may fracture or bend under stress. Signs and symptoms may be bone pain, deformity, fractures, neurological disorders resulting from cranial and spinal nerve entrapment and from spinal cord and brain stem compression, increased cardiac output to the involved bone, increased serum alkaline phosphatase levels (reflecting increased bone formation) and/or urine hydroxyproline excretion (reflecting increased bone resorption).

Clinical Trials

In one double-blind clinical trial, 64 patients with moderate to severe Paget's disease of bone were enrolled to receive 5 mg, 15 mg, or 30 mg of Aredia as a single 4-hour infusion on 3 consecutive days, for total doses of 15 mg, 45 mg, and 90 mg of Aredia.

The mean baseline serum alkaline phosphatase levels were 1,409 U/L, 983 U/L, and 1,085 U/L, and the mean baseline urine hydroxyproline/creatinine ratios were 0.25, 0.19, and 0.19 for the 15-mg, 45-mg, and 90-mg groups, respectively.

The effects of Aredia on serum alkaline phosphatase (SAP) and urine hydroxyproline/creatinine ratios (UOHP/C) are summarized in the following table.

Percent of Patients With Significant % Decreases in SAP and UOHP/C

Bookmark this page: