Hypercalcemia (PDQ®): Supportive care - Health Professional Information [NCI] - Management
The use of subcutaneous (SC) administration of clodronate has been explored. Initial experience suggested that clodronate was well tolerated subcutaneously; however, aminobisphosphonates such as pamidronate resulted in local irritation. In a subsequent study, 37 inpatients with terminal cancer received 45 clodronate infusions.[Level of evidence: II] Clodronate, 1,500 mg in 1 L of normal saline, was administered via a 23-gauge, ¾-inch butterfly needle into the SC space. All the infusions were completed, and none required discontinuation due to discomfort. The authors concluded that their results suggested that SC clodronate is an effective treatment for hypercalcemia of malignancy and is associated with minimal toxicity. This technique has advantages in the care of terminally ill patients at home and may avoid the need for hospital admission and/or IV administration. In addition, SC administration in the hospital setting has advantages for patients for whom an IV site may be problematic.
Calcitonin and plicamycin have a more rapid hypocalcemic effect than bisphosphonates; however, pamidronate has several advantages over nonbisphosphonate therapies. In comparison with plicamycin, response rates are greater among patients treated with pamidronate.[Level of evidence: I] Pamidronate more frequently reduces serum calcium concentrations to normocalcemic ranges than either calcitonin or plicamycin.[26,27][Level of evidence: I] In addition, pamidronate's hypocalcemic effect is dose related and sustained after repeated administration, and it generally persists longer than the effects produced by either calcitonin or plicamycin therapies.[Level of evidence: I] Pamidronate lacks the renal, hepatic, and platelet toxic effects associated with plicamycin.
Calcitonin is a peptide hormone secreted by specialized cells in the thyroid and parathyroid. Its synthesis and secretion normally increase in response to high concentrations of serum-ionized calcium. Calcitonin opposes physiologic effects of parathyroid hormone on bone and renal tubular calcium resorption; however, it is not known whether calcitonin has a significant role in calcium homeostasis. Nevertheless, calcitonin rapidly inhibits calcium and phosphorous resorption from bone and decreases renal calcium reabsorption. Calcitonin derived from salmon is much more potent and is longer acting than the human hormone. The initial dose schedule is 4 IU/kg of body weight per SC dose or intramuscular (IM) dose every 12 hours. Dose and schedule may be escalated after 1 or 2 days to 8 IU/kg every 12 hours, and finally to 8 IU/kg every 6 hours if the response to lower doses is unsatisfactory. Unfortunately, tachyphylaxis commonly occurs. With repeated use, calcitonin's beneficial hypocalcemic effect wanes, even at the upper recommended limits of dose and schedule, so that its calcium-lowering effect lasts for only a few days. In patients who are responsive to calcitonin, its combination with bisphosphonates may hasten the onset and duration of a hypocalcemic response caused by calcitonin's rapid (within 2–4 hours) onset of action.[Level of evidence: II];[Level of evidence: IV]