Clinical evaluation of incadronate in korean patients with malignancy-associated hypercalcemia: An open-label, multicenter study.

Abstract.

BACKGROUND

Incadronate has been found to lessen the increase in corrected serum calcium levels in malignancy-associated hypercalcemia (MAH) in a Phase III study in Japan. The drug is currently used to treat MAH in Japan.

OBJECTIVE

The purpose of this study was to assess the clinical usefulness of incadronate in patients with MAH.

METHODS

This open-label study was conducted at 3 medical institutions in Korea. Korean patients with MAH (corrected serum calcium levels ≥11.0 mg/dL) were given a single 10-mg IV infusion of incadronate over 2 to 4 hours in 500 to 1000 mL of normal saline. Corrected calcium levels were determined and subjective symptoms and objective findings (ie, bone pain, spontaneous pain, pain from contusion, tenderness, other pain, loss of appetite, nausea and/or vomiting, thirst, constipation, fatigue, and disturbance of consciousness) were used to monitor the effectiveness of the drug for 6 days after the infusion. Symptoms were evaluated using a 4-point scale (0 = none to 3 = severe). Adverse events (AEs) were identified by patients' reports, and adverse drug events (ADEs) were assessed by the investigators throughout the study.

RESULTS

Twenty-four Korean patients (18 [75%]male, 6 [25%]female; mean age, 56.5 years) were included in the study; data from 22 and 24 patients were used to assess effectiveness and tolerability, respectively. Corrected serum calcium level was significantly decreased on day 6 after treatment compared with pretreatment on day 0 (baseline) (9.51 [0.89] mg/dL vs 11.83 [0.89] mg/dL; P < 0.001). The antihypercalcemic effect of incadronate became apparent as an inhibition of bone absorption a few days after infusion. Corrected serum calcium level was significantly decreased on days 2 to 6 (P < 0.001) after treatment compared with pretreatment at baseline. Evaluation of symptoms showed significant improvement in the incadronate-treated group (mean total score [range] at baseline, 8 [1-23] and day 6, 5.5 [1-17]; P = 0.001). Eight (33.3%) of the patients were found to have ADEs. Some of the 8 patients experienced >1 ADE (mild and transient fever [13 events], chills [3], headache [1], and myalgia [1]). AEs were observed in 19 (79.2%) of 24 patients. The most frequently reported AE was fever (14 events).

CONCLUSIONS

In this small, open-label study, Korean subjects with MAH treated with incadronate experienced significant improvement in symptoms and calcium levels from baseline.