Denosumab in hypercalcemia of malignancy: a case series.

BACKGROUND: Denosumab is a nuclear factor-kappa ligand monoclonal antibody whose FDA-approved indications include treatment of osteoporosis, bone loss with certain anticancer hormonal agents, and prevention of skeletal-related events in patients with bone metastases from solid tumors. In clinical trials, the incidence of severe hypocalcemia has been reported as 3.1-10.8%. To date, case reports and two clinical trials have reported the use of denosumab in the management of hypercalcemia of malignancy. No reports of denosumab-induced hypocalcemia have been reported for the hypercalcemia of malignancy population. METHODS: We performed a retrospective chart review of all patients who received denosumab for hypercalcemia of malignancy to describe the effects of denosumab on calcium levels at our institution. RESULTS: Seven patients received doses of denosumab for hypercalcemia of malignancy. The most common tumor types were breast cancer (n = 3) and hematologic malignancies (n = 2). All patients had bone involvement. Two patients received single doses of 60 mg. The other five patients received 120 mg. The mean corrected calcium levels were 13.7 mg/dL and 12.24 mg/dL for the days of admission and denosumab administration, respectively (p = 0.1889). The mean corrected calcium level for the last known value was 9.92 mg/dL, while in house (p = 0.0016). Supportive care prior to denosumab included hydration (n = 7), bisphosphonates (n = 6), and calcitonin (n = 5). One patient had a calcium level of 6.6 mg/dL on day 4 after denosumab, requiring calcium supplementation and telemetry. Of the seven patients treated with denosumab for hypercalcemia of malignancy at our institution, six patients were discharged alive. Of these, one patient died two days after discharge. Last-known follow-up was a median of 26 days, range, 3-195, for all patients. CONCLUSIONS: Denosumab helped decrease calcium in patients with hypercalcemia of malignancy. However, symptomatic hypocalcemia may result from denosumab in hypercalcemia of malignancy.

A targeted peritransplant antifungal strategy for the prevention of invasive fungal disease after lung transplantation: a sequential cohort analysis.

BACKGROUND: Lung transplant recipients are at high risk of invasive fungal disease (IFD), particularly invasive aspergillosis and candidiasis. The antifungal strategy that optimally balances effective reduction of IFD with a minimum of toxicity remains undefined; universal triazole prophylaxis is common at lung transplantation (LT) centers, despite the well-known toxicities and costs of this approach. METHODS: We implemented an antifungal strategy in March 2007 targeted at LT recipients at highest risk for IFD based on our institutional epidemiology. All patients received inhaled amphotericin B during their initial LT hospitalization, bilateral lung transplant recipients received 7 to 10 days of micafungin, and only patients with growth of yeast or mold in their day-of-transplant cultures received further oral antifungal therapy tailored to their fungal isolate. RESULTS: IFD events were assessed in sequential cohorts composed of 82 lung transplant recipients before and 83 patients after the implementation of this targeted antifungal strategy. We observed a sharp decline in IFD; in the second cohort, 87%, 91%, and 96% of patients were free of IFD, invasive candidiasis, and invasive aspergillosis at 1 year. Only 19% of patients in the second cohort received systemic antifungal therapy beyond the initial LT hospitalization, and no patients experienced antifungal drug-related toxicity or IFD-associated mortality. CONCLUSIONS: The targeted antifungal strategy studied seems to be a reasonable approach to reducing post-LT IFD events while limiting treatment-related toxicities and costs.