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 Titration of Androgen Signaling: How Basic Studies Have Informed Clinical Trials Using High-Dose Testosterone Therapy in Castrate-Resistant Prostate Cancer

Life ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 884
Author(s):  
Steven K. Nordeen ◽  
Lih-Jen Su ◽  
Gregory A. Osborne ◽  
Perry M. Hayman ◽  
David J. Orlicky ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Dose ◽  
Castration Resistant Prostate Cancer ◽  
Androgen Ablation ◽  
Clinical Observations ◽  
Clinical Benefits ◽  
Castrate Resistant Prostate Cancer ◽  
Prostate Cancers ◽  
Castrate Resistant ◽  
Basic Studies

Since the Nobel Prize-winning work of Huggins, androgen ablation has been a mainstay for treatment of recurrent prostate cancer. While initially effective for most patients, prostate cancers inevitably develop the ability to survive, grow, and metastasize further, despite ongoing androgen suppression. Here, we briefly review key preclinical studies over decades and include illustrative examples from our own laboratories that suggest prostate cancer cells titrate androgen signaling to optimize growth. Such laboratory-based studies argue that adaptations that allow growth in a low-androgen environment render prostate cancer sensitive to restoration of androgens, especially at supraphysiologic doses. Based on preclinical data as well as clinical observations, trials employing high-dose testosterone (HDT) therapy have now been conducted. These trials suggest a clinical benefit in cancer response and quality of life in a subset of castration-resistant prostate cancer patients. Laboratory studies also suggest that HDT may yet be optimized further to improve efficacy or durability of response. However, laboratory observations suggest that the cancer will inevitably adapt to HDT, and, as with prior androgen deprivation, disease progression follows. Nonetheless, the adaptations made to render tumors resistant to hormonal manipulations may reveal vulnerabilities that can be exploited to prolong survival and provide other clinical benefits.

A castrate-resistant metastatic prostate cancer patient with severe pancytopenia, successfully treated with docetaxel chemotherapy

2019 ◽  
Vol 26 (5) ◽  
pp. 1254-1258
Author(s):  
Anuradha Kunthur
Keyword(s):  
Prostate Cancer ◽  
Bone Marrow ◽  
Prostate Specific Antigen ◽  
Bone Marrow Involvement ◽  
Specific Antigen ◽  
Docetaxel Treatment ◽  
Castrate Resistant Prostate Cancer ◽  
Severe Pancytopenia ◽  
Castrate Resistant ◽  
Docetaxel Chemotherapy

Introduction Prognosis of metastatic castrate-resistant prostate cancer is poor with a median survival of 12 to 36 months. Bone metastasis is common, and bone marrow metastasis occurs later in the disease course. The median survival in these patients after bone marrow involvement is less than six months. We report a case of castrate-resistant prostate cancer patient presented with severe pancytopenia due to bone marrow involvement of prostate cancer, treated successfully with docetaxel chemotherapy. Post chemotherapy, the patient became transfusion independent and prostate-specific antigen improved to 0.1 ng/ml from 1051 ng/ml. Case report A 70-year-old gentleman with a history of metastatic prostate cancer on androgen deprivation therapy and polycythemia vera presented to emergency room with dizziness and melena. Workup revealed severe pancytopenia with platelet count of 12k and hemoglobin of 4.5 gm/dl. Bone marrow biopsy confirmed diffuse involvement of bone marrow with prostate cancer. Prostate-specific antigen was 1051 gm/dl. Management and outcome: The patient received 14 units of packed red blood cell, 10 units of platelet transfusion within one week. Docetaxel chemotherapy was started along with thrombopoietin agonist romiplostim and pegylated filgrastim. He received five cycles of docetaxel treatment. Post chemotherapy, the patient became transfusion independent and prostate-specific antigen improved to 1.17 ng/ml from 1051 ng/ml. The patient is still alive one year after the presentation with good quality of life and the prostate-specific antigen further improved to 0.1 ng/dl. Conclusion This case suggests that selected patients with severe pancytopenia, due to bone marrow infiltration of prostate cancer, can be treated with docetaxel chemotherapy and romiplostim support with significant response. Docetaxel treatment may be beneficial to unpack the marrow and for quicker response in patients with good performance status.

Abiraterone and Increased Survival in Metastatic Prostate Cancer

2021 ◽  
pp. 95-100
Author(s):  
Joseph Zabell
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Adverse Effects ◽  
Metastatic Prostate Cancer ◽  
Prior Chemotherapy ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

This chapter summarizes the findings of a landmark trial conducted in men with castrate-resistant prostate cancer who had received prior chemotherapy comparing abiraterone to placebo. It demonstrated improved progression-free and overall survival. It was relatively well tolerated, with most adverse effects related to mineralocorticoid excess.

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.

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