SAT-498 Use of Cinacalcet for PTHrP-Mediated Hypercalcemia of Malignancy in Penile Squamous Cell Carcinoma

Background: PTHrP-mediated hypercalcemia accounts for 80% of hypercalcemia of malignancy (HCM), and is traditionally treated with bisphosphonates or hemodialysis. We report a patient with penile squamous cell carcinoma (SCC) and bisphosphonate resistant PTHrP-mediated HCM that responded to calcimimetic therapy. Clinical Case: A 75-year-old man with metastatic penile SCC was admitted with altered sensorium. He had no prior history of hypercalcemia or fractures. His exam was significant for disorientation and hypovolemia. Labs revealed an elevated ionized calcium [iCa] of 1.65 mmol/L [0.95-1.32 mmol/L], phosphorus 2.6 mg/dl [2.5-4.6 mg/dL], magnesium 1.8 mg/dl [1.6-2.7 mg/dL], appropriately low intact PTH 8.1 pg/ml [8.0-85.0 pg/mL], 25-hydroxy vitamin D of 24 ng/ml [30-100 ng/mL], TSH 3.3 uIU/mL [0.350-4.940 uIU/mL], elevated PTHrP level 47 pg/ml [14-27 pg/mL], 1, 25-dihydroxy vitamin D 25 pg/ml [18 - 64 pg/mL], and serum immunofixation negative for paraproteins. Due to concomitant SIADH, intravenous (IV) fluids were used cautiously. He received IV zoledronic acid (ZA) 4mg on Day 2, following which iCa normalized in two days. One month later, the patient was readmitted with pneumonia. On Day 7, he was noted to have an elevated iCa of 1.4 mmol/L. On Day 8 of admission, he was given a second dose of IV ZA 4mg and iCa normalized 48 hours later. However, his hospital course was complicated by recurrences of hypercalcemia on day 14 (iCa 1.41 mmol/L) and day 24 (iCa 1.41 mmol/L) requiring 2 additional doses of IV ZA 4mg (Days 14 and 24) resulting in brief normalization of iCa. On day 26, iCa increased to 1.36 with further ZA unable to be administered due to worsening creatinine clearance. Use of IV fluids was limited due to worsening hyponatremia. Denosumab or calcitonin were not available in the inpatient formulary. Prior to considering hemodialysis, the patient was started on a trial of oral cinacalcet 30mg daily on Day 28. Within 24 hrs of initiation of cinacalcet, iCa normalized. On Day 40 hemodialysis was initiated. iCa increased to 1.36 on Day 43 requiring 60 mg of cinacalcet daily. Throughout the remainder of the patient’s hospitalization, further titration of cinacalcet was required with 90 mg twice daily prescribed on Day 54 resulting in normalization of iCa. On day 60, iCal was again found to be abnormal with a repeat PTHrP level of 1318 pg/ml. iCal levels continued to trend up until day 64, when the patient had a cardiac arrest and expired. Conclusion: Cinacalcet is an allosteric activator of the calcium sensing receptor. The mechanism of effect on PTHrP-mediated HCM is still under investigation, but in murine models, increased calcitonin secretion appears to play a role. The use of cinacalcet for HCM has been described in only four prior case reports. Further studies are needed to further elucidate the role of cinacalcet as a therapeutic option in HCM.