scholarly journals Denosumab Induced Severe Prolonged Hypocalcemia in Metastatic Prostate Cancer

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A190-A190
Author(s):  
Hassan Mehmood ◽  
Farhad Hasan
Keyword(s):  
Prostate Cancer ◽  
Vitamin D ◽  
Calcium Carbonate ◽  
Serum Calcium ◽  
Calcium Gluconate ◽  
Metastatic Prostate Cancer ◽  
High Dose ◽  
Appendicular Skeleton ◽  
Qtc Interval ◽  
Oral Calcium

Abstract Background: Denosumab is a RANK-l inhibitor that, in addition to the treatment of osteoporosis, is used in patients with advanced cancer and metastatic bone disease to prevent skeletal-related events. Although denosumab is generally safe and effective, it can cause hypocalcemia which in some patients can be severe and life threatening. We present a case of severe prolonged hypocalcemia after a single dose of denosumab in a patient with metastatic prostate cancer. Case: A 78-year-old male with a past medical history of stage 4 prostate cancer on antiandrogen treatment with GnRH antagonist presented with severe hypocalcemia. Physical exam revealed a blood pressure 125/80 mm Hg, pulse 115 per min and weight 135 lb with negative Chvostek’s and Trousseau’s signs. The electrocardiogram showed supraventricular tachycardia with prolonged QTc interval of 503 ms (<430 ms). Labs showed serum calcium 4.9mg/dL (8.5–10.5), albumin 2.5g/dL (3.6–5.1), corrected calcium 5.7 mg/dL, ionized serum calcium 0.64mmol/L (1.05–1.3), creatinine 1.10mg/dL (0.7–1.2), eGFR >60, phosphorus 2.0mg/dL (2.5–4.5), magnesium 1.9 mg/dL (1.6–2.6), 25-OH vitamin D 29.7 ng/mL (30–100), 1,25 dihydroxy vitamin D 174 pg/mL (18–64), iPTH 244.0 pg/mL (11–68) and PSA 1860 ng/mL. Three weeks prior to presentation, the patient received 120 mg of subcutaneous denosumab. Pre-treatment serum calcium was 9.2 mg/dL (8.5–10.5), and Tc-99m bone scan showed multiple osteoblastic osseous metastatic lesions involving both axial and appendicular skeleton. The patient was diagnosed with denosumab-induced severe hypocalcemia and started on intravenous (IV) calcium gluconate infusion, oral phosphate 250 mg twice daily, and ergocalciferol 50,000 IU twice weekly. He required IV calcium gluconate up to 10 g per day in addition to oral calcium carbonate 2 g t.i.d. for 2 weeks to resolve hypocalcemia and normalize QTc interval. Patient was discharged to nursing home on calcium carbonate 2 g q.i.d. with IV calcium gluconate as needed to keep corrected calcium >8.0 mg/dL. After discharge he required up to 4 g of IV calcium and 8 g of oral calcium per day. Unfortunately, he presented again with severe hypocalcemia 5 weeks after discharge. In addition to current regimen of oral and IV calcium boluses, low dose calcitriol was started. We were only able to maintain his serum calcium>8.0 mg/dL by administering high daily dose of oral calcium carbonate 8 g /day and calcitriol 2 mcg daily. Due to poor prognosis, he was transitioned to hospice care and died 2 weeks later. Discussion: There are not many case reports on severe prolonged hypocalcemia secondary to denosumab in cancer patients but normal kidney function. Our patient remained on high dose of calcium even 101 days after denosumab administration. Reference: 1. Milat F et al. Prolonged hypocalcemia following denosumab therapy in metastatic hormone refractory prostate cancer. Bone. 2013 Aug 1;55(2):305–8.

scholarly journals SAT-070 Nutritional Deficiency of Calcium Mimicking P Seudohypoparathyroidism

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Yoonji Lee ◽  
Moon Bae Ahn ◽  
Na yeong Lee ◽  
Seonhwa Lee ◽  
Yujung choi ◽  
...  
Keyword(s):  
Vitamin D ◽  
Calcium Carbonate ◽  
Serum Calcium ◽  
Calcium Absorption ◽  
Clinical Manifestations ◽  
Nutritional Deficiency ◽  
Serum Phosphorus ◽  
Vitamin D Metabolism ◽  
Laboratory Findings ◽  
Oral Calcium

Abstract BACKGROUND: Childhood hypocalcemia in general is caused by problems associated with calcium absorption and excretion, parathyroid hormone (PTH) secretion, and vitamin D metabolism. Clinical manifestations can vary from asymptomatic hypocalcemia to life-threatening conditions including convulsions, tetany and laryngeal spasm. As many symptoms are nonspecific, laboratory tests are essential for diagnosis. Nevertheless, the causes of hypocalcemia may not be determined by simple interpretation of baseline calcium, phosphorus, alkaline phosphatase (ALP), PTH and calcidiol (25OHD). Case presentation: We report a case of 11-month-old female with a generalized tonic type seizure with low serum calcium level (5.7 mg/dl), 25OHD (23.2 ng/mL) and calcitriol (1,25OH2D) (12.83 pg/mL). Serum phosphorus (5.9 mg/dL), ALP (209 mg/dL) were above normal range and PTH (484 pg/mL) was markedly elevated. She had a problem with weaning process after age of 5 months and milk powder was her main staple diet. Pseudohypoparathyroidism (PHP) was suspected due to slightly increased serum phosphorus, however Albright’s hereditary osteodystrophy manifestation was absent and no GNAS methylation defect was identified. Serum calcium was normalized by intravenous calcium-gluconate followed by oral calcium carbonate and vitamin D supplement. Two months of oral oral calcium carbonate and vitamin D supplementation alone normalized all laboratory results. Conclusions: Severe nutritional deficiency of calcium could mimic laboratory findings of PHP, therefore clinical judgement should not be made solely on biochemical markers. Keywords: Hypocalcemia, pseudohypoparathyroidism, rickets 제1저자: Yoonji Lee, Moonbae Ahn, Na yeong Lee, Seonhwa Lee, Yujung Choi, Seulki Kim, Shinhee Kim, Wonkyoung Cho, Kyoungsoon Cho, Minho Jung, and Byungkyu Suh* Department of Pediatrics, College of Medicine, Catholic University of Korea

scholarly journals Denosumab-induced hypocalcaemia in metastatic castrate-resistant prostate cancer

2019 ◽  
Vol 2019 ◽  
Author(s):  
Florence Gunawan ◽  
Elizabeth George ◽  
Mark Kotowicz
Keyword(s):  
Prostate Cancer ◽  
Vitamin D ◽  
Adverse Effects ◽  
Serum Calcium ◽  
Serum Alkaline Phosphatase ◽  
Bone Marrow Involvement ◽  
High Dose ◽  
List Type ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

Summary Denosumab is a fully human MAB that acts as a potent anti-resorptive by inhibiting activation of osteoclasts by inhibiting the receptor activator of nuclear factor-kappa B (RANK) ligand. Hypocalcaemia has been reported as one of the serious adverse sequelae of use of denosumab. We present a case of refractory hypocalcaemia following administration of a single dose of denosumab in a patient with metastatic castrate-resistant prostate cancer. The patient’s serum calcium and vitamin D concentrations and renal function were normal prior to denosumab administration. Serum alkaline phosphatase (ALP) level was however elevated pre-morbidly consistent with known bone metastases. The patient was treated with high-dose oral and IV calcium without any appreciable response in serum calcium. During his 30-day hospital admission, he demonstrated disease progression with development of new liver metastases and bone marrow involvement. Normocalcaemia was not achieved despite 1 month of aggressive therapy. Given the patient was asymptomatic and prognosis guarded, he was eventually discharged for ongoing supportive care under the palliative care team. Learning points: Denosumab is a potent anti-resorptive therapy and hypocalcaemia is one of the known adverse effects. Serum calcium and vitamin D concentrations must be replete prior to administration of denosumab to reduce the risk of hypocalcaemia. Denosumab has been proven to be more effective than zoledronic acid in preventing skeletal-related adverse effects in patients with metastatic castrate-resistant prostate cancer.

scholarly journals Severe Hypocalcemia and Vitamin D Deficiency in Adolescence - A Case Series

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A220-A220
Author(s):  
Rachel Rothstein ◽  
Natalie Allen
Keyword(s):  
Vitamin D ◽  
Calcium Carbonate ◽  
Vitamin D Deficiency ◽  
Calcium Gluconate ◽  
Sun Exposure ◽  
Urgent Care ◽  
Restricted Diet ◽  
Oral Calcium ◽  
X Ray ◽  
History Of

Abstract Background: Hypocalcemia due to vitamin D (vit D) deficiency is uncommon among adolescents in the US. Only 3% to 6% of those ages 12- to 19-years-old have a vit D level <12 ng/ml.1 We present three cases of severe hypocalcemia secondary to vit D deficiency in non-obese adolescents with restricted diets and limited sun exposure. Clinical Cases: A 14-year-old Ethiopian male with history of absence seizures presented with bloody stool. Incidentally, labs revealed: Ca 5.6 (8.4–10.2) mg/dL, iCal 0.71 (1.2–1.38) mmol/L, PTH 295.1 (10.0–65.0) pg/mL, 25(OH)D <4 (20–100) ng/mL, Mg 1.9 (1.7–2.2) mg/dL, PO4 3.8 (2.5–4.5) mg/dL. He endorsed weight loss and knee pain, but denied paresthesias, tetany and seizures. He was a vegetarian and had minimal sun exposure. EKG and femur X-ray were unremarkable. He was started on IV calcium gluconate initially. Oral calcium carbonate and cholecalciferol were started on days three and four. He was discharged on day ten with iCal 0.84 on oral calcium carbonate and calcitriol. A 16-year-old male with history of autism, ADHD and bipolar disorder presented with a seizure. Labs revealed: Ca 5.7, iCal 0.62, PTH 372, 25(OH)D <4, Mg 1.9, PO4 3.5. Exam showed tetany, carpopedal spasms and positive Trousseau and Chvostek signs. EKG revealed prolonged QTc of 480 (<450) ms. He had a restricted diet and minimal sun exposure. His mother described his gait as “waddling” for the past two years. X-ray revealed bilateral femoral head fractures and evidence of rickets. He underwent bilateral surgical repair. He was started on IV calcium gluconate initially. Oral calcium carbonate and cholecalciferol were started on days two and four. He was discharged on day 14 with iCal 1.01 on oral calcium carbonate and cholecalciferol. A 16-year-old male with history of severe food allergies and restricted diet presented with a seizure. He visited urgent care three months prior for perioral tingling, muscle cramps and chest pain. He started a multivitamin for “low Ca” and “prolonged QTc.” The ED labs revealed: Ca 4.8, PTH 414.8, 25(OH)D 11, Mg 1.9, PO4 5.0, Alk Phos 539 (44–147) IU/L. Exam showed upper extremity twitching and QTc was 543 ms. He received 2 g calcium gluconate IV, then began oral calcium carbonate and cholecalciferol and continued supplementation following discharge on day six. Conclusions: Vit D deficiency among adolescents is re-emerging, likely due to decreasing sun exposure, unbalanced diets and increasing obesity.2 Adolescents with restricted diets due to allergy or behavioral disorders may be at higher risk of vit D deficiency. Increased screening of high-risk adolescents may lead to early identification of cases. References: 1) Palacios, C., et al. Is vitamin D deficiency a major global public health problem? J Steroid Biochem Mol Biol. 2013;144PA;138-145 2) Antonucci, R., et al. Vitamin D deficiency in childhood: old lessons and current challenges. J Pediatr Endocrinol Metab. 2018;31(3);247–260.

Phase IB trial redesign to test role of IL2 with anti-PSMA designer T cells to yield responses in advanced prostate cancer.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 70-70 ◽  
Author(s):  
Richard P. Junghans
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
T Cells ◽  
Metastatic Prostate Cancer ◽  
Immune Therapy ◽  
High Dose ◽  
Activated T Cells ◽  
Phase Ib ◽  
Cell Dose

70 Background: We created a chimeric antigen receptor (CAR) for prostate specific membrane antigen (PSMA). When expressed in patient T cells, these “designer T cells” specifically kill prostate cancer cells in vitro and in vivo in animal models (Ma et al. Prostate 2004:61:12-25). FDA approved a Phase I clinical trial. Methods: Patient T cells are retrovirally transduced and expanded. Patients undergo non-myeloablative (NMA) conditioning to create “hematologic space” into which designer T cells are infused for engraftment and improved in vivo efficacy. Patients are co-administered continuous infusion IL2. Patients are monitored for safety and response. Results: Five patients were treated, three at 10^9 and two at 10^10 cell dose levels with safety. Partial responses (PR) were seen in 2/5 patients (40%), with PSA suppressions of 50 and 70% over 1-2 months and PSA progression delay of 70 and 150 days. Yet these responses were observed only at the lowest T cell dose (10^9 cells) and not the higher tested dose (10^10 cells). Response correlated with plasma IL2 that was as much as 10-fold lower in non-responders vs responders. This low IL2 correlated in turn with high engrafted fractions of infused activated T cells. This prompted a hypothesis that infused activated T cells at high engrafted cell numbers absorbed out IL2 to a level too low to sustain dTc activation for effective tumor killing. A study redesign will test high dose IL2 (HDI) versus moderate dose IL2 (MDI) in Phase Ib/Pilot at 10^10 cell dose, then advancing to the maximum practical dose (MPD, 10^11 cells) of dTc under the optimal IL2 plan. Conclusions: A new approach to adoptive immune therapy in metastatic prostate cancer has been devised with encouraging early results. We postulate that adequate higher IL2 in vivo will allow the greater potency of higher dTc doses to be revealed, thereby potentially inducing PSA reductions of 100%, with durable remissions of metastatic prostate cancer that is refractory to all other treatments. Patients are being recruited. This clinical trial received funding from US Army/DOD and from Prostate Cancer Foundation for preclinical work.

Leucovorin and High-Dose Fluorouracil in Metastatic Prostate Cancer

1996 ◽  
Vol 19 (1) ◽  
pp. 23-25 ◽  
Author(s):  
James N. Atkins ◽  
Hyman B. Muss ◽  
L. Douglas Case ◽  
Frederick Richards ◽  
Thomas Grote ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
High Dose
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