Single-dose intravenous therapy with pamidronate for the treatment of hypercalcemia of malignancy: comparison of 30-, 60-, and 90-mg dosages.
OBJECTIVE
To determine the efficacy, dose-response relationship, and safety of 30, 60, and 90 mg of a single intravenous dose of an aminobisphosphonate, pamidronate (APD), for the treatment of moderate to severe hypercalcemia of malignancy.


METHODS
Patients with histologically proven cancer and a corrected serum calcium level of at least 12.0 mg/dL 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 excretion, and serum parathyroid hormone (PTH) (1-84) were determined before and after pamidronate therapy.


RESULTS
Thirty-two men and 18 women entered the study. A dose-response relationship for normalization of corrected serum calcium was seen after pamidronate administration. Corrected 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 received 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 those with a normalized 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 treatment groups, respectively. The response of hypercalcemia to pamidronate was 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 metastases compared with those with humoral hypercalcemia of malignancy. Clinical improvement, including improved mental status and decreased anorexia, accompanied the decline in the corrected serum calcium level in all three treatment groups. Side effects included low-grade fever, asymptomatic hypocalcemia, hypomagnesemia, and hypophosphatemia.


CONCLUSIONS
A single-dose infusion of 60 to 90 mg of pamidronate was highly effective and well tolerated and normalized corrected serum calcium in nearly all patients (61% to 100%) with hypercalcemia of malignancy.
Nussbaum
S R
SR
Medical Service, Massachusetts General Hospital, Boston 02114.
Younger
J
J
Vandepol
C J
CJ
Gagel
R F
RF
Zubler
M A
MA
Chapman
R
R
Henderson
I C
IC
Mallette
L E
LE
D000368:Aged; D004164:Diphosphonates / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000150:complications*; D000077268:Pamidronate; D016896:Treatment Outcome
D004164:Diphosphonates; D000077268:Pamidronate