Abstract
Objective: To evaluate risk factors for Denosumab-induced hypocalcemia in prostate cancer patients with bone metastases. Methods: In this single-arm, open-label, prospective multicenter study, 48 prostate cancer patients with bone metastases received Denosumab (120 mg on day 1) and androgen-deprivation therapy. Serum calcium, albumin, alkaline phosphatase (ALP), and phosphate levels; chronic kidney disease stage; and serum prostate specific antigen and urine N-terminal telopeptide (u-NTx) levels were examined. Patients were divided into 2 groups on the basis of whether or not they developed hypocalcemia at 1 week or 1 month after Denosumab administration. Risk factors for hypocalcemia were determined by univariate and multivariate logistic regression analysis. Results: Nineteen patients (39.6%) demonstrated hypocalcemia at 1 week after Denosumab administration, and 16 (33.3%) were hypocalcemic at 1 month. Patients with hypocalcemia at 1 week had higher baseline serum ALP levels (1283.4 ± 1489.7 [mean ± SD] vs 467.3 ± 655.8, P=0.013) than patients without hypocalcemia. Patients with hypocalcemia at 1 month had higher baseline serum ALP (1455.5 ± 1694.1, P=0.002) and u-NTx levels (190.9 ± 63.9, P=0.013) and more bone metastases (extent of disease grade ≥ 3; 10 patients, 20.8%, P=0.006) at baseline than patients without hypocalcemia. Multivariate logistic regression analysis revealed that baseline u-NTx of >100 nmol bone collagen equivalents/mmol creatinine was a significant independent risk factor for hypocalcemia (odds ratio=12.41, 95% confidence interval=1.059-145.600, P=0.049). Conclusions: Baseline u-NTx level is an independent risk factor for Denosumab-induced hypocalcemia in prostate cancer patients with bone metastases.
Highlights
Prostate cancer is diagnosed in more than 670,000 men yearly worldwide [1,2], and compared to other malignancies, urological malignancies are the most common cause of bone metastases (70– 80%) [3,4]
A fully human monoclonal antibody with high affinity and specificity for the human receptor activator of nuclear factor-κB ligand, was shown to inhibit bone re-absorption in early studies in patients with advanced cancer, including those who did not respond to prior bisphosphonate treatment [12,13,14,15], and these results suggest a potential new approach for the treatment of bone metastasis
The following patient characteristics and laboratory data were collected at baseline: age at the start of Denosumab treatment; Gleason score; androgen sensitivity status; history of treatment or prevention of skeletal-related events (SREs); serum concentrations of calcium, albumin alkaline phosphatase (ALP), phosphate and prostatic specific antigen (PSA); urine N-terminal telopeptide level; extent of disease (EOD; i.e., extent of bone metastasis on initial bone scan); and chronic kidney disease (CKD) stage
Summary
Prostate cancer is diagnosed in more than 670,000 men yearly worldwide [1,2], and compared to other malignancies, urological malignancies are the most common cause of bone metastases (70– 80%) [3,4]. Patients with bone metastases may experience local irreversible skeletal complications, including pathologic fractures and spinal cord compression, and may require bone irradiation or surgery Such complications, referred to as skeletal-related events (SREs), are indicators of poor prognosis and cause substantial pain and morbidity that frequently lead to hospitalization, poor quality of life, and increased utilization of medical resources [5,6,7,8,9]. Patients with metastatic castration-resistant prostate cancer have been living longer, owing to the advent of newer, targeted therapies [10,11] They are more likely to experience SREs and the role of bone-targeted therapies to prevent and treat SREs is becoming more important.
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