- Hypercalcemia of Malignancy (HCM) is an oncologic emergency typically seen in patients with advanced stage cancers
- HCM is more common in patients with tumors that are associated with bone metastases (breast, lung, multiple myeloma, renal cell carcinoma and colorectal cancer)
- Hypercalcemia is defined as a corrected calcium level > 10.5 mg/dL
- Symptoms occur slowly (or may be absent) and can include nephrolithiasis, polyuria, polydipsia, gout, ventricular tachyarrhythmias, fatigue, anorexia, cognitive dysfunction, etc.
- Management of hypercalcemia is traditionally with aggressive IV fluids, calcitonin, and bisphosphonates. Loop diuretics and steroids have a limited role in treatment for most patients.
|Role in Therapy||• •||Used to provide a transient decrease in serum calcium levels Used with aggressive fluid hydration and IV bisphosphonates||• Should be administered ASAP after diagnosis|
|Mechanism||•||Inhibits osteoclastic bone resorption and promotes renal excretion of calcium||• Deposits into bone and lowers calcium levels by inhibiting osteoclastic bone resorption|
|Dose||•||4 IU/kg IM/SQ Q12 hours x48 hours||Zoledronic Acid (Zometa) 4mg IV over 15-30 minutes (NO dose adjustments needed for HCM indication) SCr must be < 4.5 mg/dL Pamidronate 90 mg IV over 4 hours May use if SCr > 4.5 mg/dL|
|PK/PD||• •||Onset of action: 4-6 hours Efficacy limited to 48 hours due to tachyphylaxis||Onset of action: 48 hours (maximal effect: 2-4 days) Duration of action: 3-4 weeks|
|Adverse Effects||•||Hypersensitivity reactions (including anaphylaxis), hypocalcemia, flushing, headache, nausea/vomiting||• Renal dysfunction, osteonecrosis of the jaw, bone and joint pain|
|Comments||• •||Consider administering if corrected Ca ≥ 14 mg/dL and/or neurologic or cardiac symptoms Must administer IVF x4-6 hours and recheck Ca PRIOR to ordering||Zoledronic is more efficacious with regards to time to normalization of calcium and duration of complete response May repeat bisphosphonate dose in 7 days if needed|
|Kammerman, 1970||Case Series (n=8)||Report the efficacy of porcine calcitonin in patients with hypercalcemia||In the 7 patients given a uniform dose of 4 MRC U/kg body weight, a mean change in serum calcium concentration of −1.97 mg/dL The calcium-lowering effect was measurable at 2 hr and maximal at 6–9 hr; by 20–24 hr the serum calcium had begun to rise.|
|Thiébaud, 1990||RCT (n=34)||To assess whether a combined calcitonin and pamidronate lead to earlier normalization of the plasma calcium level than does pamidronate alone||In the group receiving calcitonin, the mean plasma calcium level decreased from 3.22 ±0.09 mmol/L to 2.29 ±0.03 mmol/L by day 9 (P<.001) and was normalized by day 3. There was a significant difference the groups in the plasma calcium level from day 2 to day 4, reflecting the earlier drop in calcium level in the group receiving calcitonin.|
|Major, 2001||RCT (n= 287)||Compare the efficacy and safety of zoledronic acid and pamidronate for treating hypercalcemia of malignancy||Zoledronic acid is superior to pamidronate with a complete response rate by day 10 (88.4% vs. 69.7%) and longer median duration of complete response (32 days vs. 18 days)|
|Hu. 2014||Open-label, single arm (n= 33)||Evaluate the efficacy of denosumab in patients with bisphosphonaterefractory HCM||Denosumab lowered calcium in 64% of patients within 10 days, with an estimated median time to response of 9 days. • FDA-approved denosumab for HCM|
|Sabry, 2010||Observational, (n=80)||Evaluate the difference in efficacy and safety of zoledronic acid and clodronate in malignant hypercalcemia secondary to bone metastases.||The calcium level significantly decreased in both groups. At least one skeletal-related event occurred in 15 (37.5%) patients receiving zoledronic acid and 32 (80%) patients receiving clodronate.|
|Hosking, 1981||Observational (n=16)||Evaluate the efficacy of rehydration (NS) in patients with hypercalcemia||A substantial fall in serum calcium (mean decrease 0.6 mmol/l) was achieved in thirteen patients.|
|Sleeboom, 1983||Observational (n=30)||Evaluate the effects of tumorinduced hypercalcemia management with volume repletion and intravenous pamidronate||Volume repletion was only partially effective in lowering serum calcium and raising glomerular filtration rate and it increased the tendency towards hypomagnesaemia. In twenty-nine of the patient’s serum calcium, serum magnesium, and glomerular filtration rate were rapidly restored to normal by intravenous pamidronate, in doses of 1.75-30 mg/day.|
- Reported in 20 – 30% of cancer patients and is a poor prognostic indicator
- Primarily associated with lung and breast cancer, as well as myeloma and lymphoma
- Presentation can range from asymptomatic to progressive mental impairment, arrhythmias, and renal failure
- Cornerstones of therapy include aggressive hydration, calcitonin, and IV bisphosphonates
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