Jean-Jacques Body1, Henry G Bone2, Richard H de Boer3, Alison Stopeck4, Catherine Van Poznak5, Ronaldo Damião6, Karim Fizazi7, David H Henry8, Toni Ibrahim9, Allan Lipton10, Fred Saad11, Neal Shore12, Toshimi Takano13, Adam J Shaywitz14, Huei Wang15, Oswaldo L Bracco16, Ada Braun17, Paul J Kostenuik18. 1. Department of Medicine, CHU Brugmann, Université Libre de Bruxelles, Brussels, Belgium. Electronic address: jean-jacques.body@chu-brugmann.be. 2. Michigan Bone and Mineral Clinic, Detroit, MI, USA. Electronic address: hgbone.md@att.net. 3. Department of Medical Oncology, Royal Melbourne Hospital, Melbourne, VIC, Australia. Electronic address: richard.deboer@wh.org.au. 4. Stony Brook Cancer Center, Stony Brook, NY, USA. Electronic address: Alison.Stopeck@stonybrookmedicine.edu. 5. Department of Medical Oncology, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, USA. Electronic address: cvanpoz@med.umich.edu. 6. Department of Urology, Hospital Universitario Pedro Ernesto, Rio de Janeiro, Brazil. Electronic address: damiao@email.com. 7. Department of Medical Oncology, Institut Gustave Roussy, University of Paris Sud, Villejuif, France. Electronic address: Karim.FIZAZI@igr.fr. 8. Department of Medicine, Joan Karnell Cancer Center at Pennsylvania Hospital, Philadelphia, PA, USA. Electronic address: dhhenry@juno.com. 9. Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS-Osteoncology and Rare Tumors Center, Meldola, Italy. Electronic address: toni.ibrahim@irst.emr.it. 10. Division of Oncology, Pennsylvania State University, Milton S. Hershey Medical Center, Hershey, PA, USA. Electronic address: alipton@hmc.psu.edu. 11. Department of Surgery, University of Montreal Hospital Center, Montreal, QC, Canada. Electronic address: fredsaad@videotron.ca. 12. Department of Urology, Carolina Urologic Research Center, Myrtle Beach, SC, USA. Electronic address: nshore@gsuro.com. 13. Department of Medical Oncology, Toranomon Hospital, Tokyo, Japan. Electronic address: takano@toranomon.gr.jp. 14. Department of Hematology/Oncology, Amgen Inc., Thousand Oaks, CA, USA. Electronic address: ashaywitz@gmail.com. 15. Department of Hematology/Oncology, Amgen Inc., Thousand Oaks, CA, USA. Electronic address: hueiw@amgen.com. 16. Department of Hematology/Oncology, Amgen Inc., Thousand Oaks, CA, USA. Electronic address: ozzie.bracco@gmail.com. 17. Department of Hematology/Oncology, Amgen Inc., Thousand Oaks, CA, USA. Electronic address: adahbraun@yahoo.de. 18. Department of Hematology/Oncology, Amgen Inc., Thousand Oaks, CA, USA. Electronic address: PKost@roadrunner.com.
Abstract
BACKGROUND: This analysis was performed to further characterise treatment-emergent hypocalcaemia in patients with bone metastases receiving denosumab. METHODS: Laboratory abnormalities and adverse events of hypocalcaemia in patients with metastatic bone disease were analysed using data from three identically designed phase 3 trials of subcutaneous denosumab 120 mg (n = 2841) versus intravenous zoledronic acid 4 mg (n = 2836). RESULTS: The overall incidence of laboratory events of hypocalcaemia grade ⩾ 2 was higher with denosumab (12.4%) than with zoledronic acid (5.3%). Hypocalcaemia events were primarily grade 2 in severity and usually occurred within the first 6 months of treatment. Patients who reported taking calcium and/or vitamin D supplements had a lower incidence of hypocalcaemia. Prostate cancer or small-cell lung cancer, reduced creatinine clearance and higher baseline bone turnover markers of urinary N-telopeptide of type I collagen (uNTx; > 50 versus ⩽ 50 nmol/mmol) and bone-specific alkaline phosphatase (BSAP; > 20.77 μg/L [median] versus ⩽ 20.77 μg/L) values were important risk factors for developing hypocalcaemia. The risk associated with increased baseline BSAP levels was greater among patients who had > 2 bone metastases at baseline versus those with ⩽ 2 bone metastases at baseline. CONCLUSION: Hypocalcaemia was more frequent with denosumab versus zoledronic acid, consistent with denosumab's greater antiresorptive effect. Low serum calcium levels and potential vitamin D deficiency should be corrected before initiating treatment with a potent osteoclast inhibitor, and corrected serum calcium levels should be monitored during treatment. Adequate calcium and vitamin D intake appears to substantially reduce the risk of hypocalcaemia.
BACKGROUND: This analysis was performed to further characterise treatment-emergent hypocalcaemia in patients with bone metastases receiving denosumab. METHODS: Laboratory abnormalities and adverse events of hypocalcaemia in patients with metastatic bone disease were analysed using data from three identically designed phase 3 trials of subcutaneous denosumab 120 mg (n = 2841) versus intravenous zoledronic acid 4 mg (n = 2836). RESULTS: The overall incidence of laboratory events of hypocalcaemia grade ⩾ 2 was higher with denosumab (12.4%) than with zoledronic acid (5.3%). Hypocalcaemia events were primarily grade 2 in severity and usually occurred within the first 6 months of treatment. Patients who reported taking calcium and/or vitamin D supplements had a lower incidence of hypocalcaemia. Prostate cancer or small-cell lung cancer, reduced creatinine clearance and higher baseline bone turnover markers of urinary N-telopeptide of type I collagen (uNTx; > 50 versus ⩽ 50 nmol/mmol) and bone-specific alkaline phosphatase (BSAP; > 20.77 μg/L [median] versus ⩽ 20.77 μg/L) values were important risk factors for developing hypocalcaemia. The risk associated with increased baseline BSAP levels was greater among patients who had > 2 bone metastases at baseline versus those with ⩽ 2 bone metastases at baseline. CONCLUSION: Hypocalcaemia was more frequent with denosumab versus zoledronic acid, consistent with denosumab's greater antiresorptive effect. Low serum calcium levels and potential vitamin D deficiency should be corrected before initiating treatment with a potent osteoclast inhibitor, and corrected serum calcium levels should be monitored during treatment. Adequate calcium and vitamin D intake appears to substantially reduce the risk of hypocalcaemia.
Authors: Subrata K Pore; Eun-Ryeong Hahm; Su-Hyeong Kim; Krishna B Singh; Lea Nyiranshuti; Joseph D Latoche; Carolyn J Anderson; Juraj Adamik; Deborah L Galson; Kurt R Weiss; Rebecca J Watters; Boeun Lee; Prashant N Kumta; Shivendra V Singh Journal: Mol Cancer Ther Date: 2019-11-29 Impact factor: 6.261
Authors: D Miyaoka; Y Imanishi; M Ohara; N Hayashi; Y Nagata; S Yamada; K Mori; M Emoto; M Inaba Journal: Osteoporos Int Date: 2018-09-05 Impact factor: 4.507