Denosumab should be the treatment of choice for bisphosphonate refractory hypercalcaemia of malignancy.
Denosumab, a fully humanised monoclonal antibody, is licensed for treatment of postmenopausal osteoporosis, hormone ablation-induced bone loss and for prevention of skeleton-related events in patients with bone metastases from solid tumours. In pivotal phase 3 randomised trials, denosumab caused profound hypocalcaemia in patients with normocalcaemia despite oral calcium and vitamin D supplementation. This significant hypocalcaemic effect can be exploited to treat hypercalcaemia of malignancy (HCM). Recent reports from the USA suggest that denosumab is an effective treatment of HCM. According to our knowledge, we report the first two cases in UK with bisphosphonate refractory hypercalcaemia who responded to denosumab injections. Our first case gained 7 months of stabilisation of hypercalcaemia following prolonged admissions with life-threatening levels, while our second case achieved rapid normalisation of serum calcium levels for the first time in 14 months. We conclude that denosumab should be the treatment of choice for patients with bisphosphonate refractory hypercalcaemia.
Department of Oncology, Nottingham City Hospital, Nottingham, UK.
Jason
J
Adhikaree
Yvette
Y
Newby
Santhanam
S
Sundar
D018262:Adenocarcinoma, Clear Cell / Q000150:complications / Q000556:secondary*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000150:complications / Q000556:secondary*; D002291:Carcinoma, Papillary / Q000150:complications / Q000556:secondary*; D002292:Carcinoma, Renal Cell / Q000150:complications / Q000556:secondary*; D000069448:Denosumab; D004164:Diphosphonates; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000188:drug therapy* / Q000209:etiology; D007680:Kidney Neoplasms / Q000150:complications / Q000473:pathology*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000150:complications / Q000473:pathology*; D010257:Paraneoplastic Syndromes / Q000188:drug therapy* / Q000209:etiology; D053245:RANK Ligand / Q000037:antagonists & inhibitors*
D061067:Antibodies, Monoclonal, Humanized; D004164:Diphosphonates; D053245:RANK Ligand; D000069448:Denosumab