Bisphosphonate selection and dosing shouldn’t be too taxing in the management of patients with hypercalcemia of malignancy with new research showing that zoledronic acid 4 mg, pamidronate 60 mg, and pamidronate 90 mg are equally efficacious in serum calcium normalisation.
A retrospective study from the Mayo Clinic comprised 856 patients, with a confirmed malignancy and a baseline serum calcium of >10.3 mg/dL, prescribed a bisphosphonate during a hospital admission between January 1, 2018, and January 31, 2024.
Underlying diagnoses included lymphoma (18.5%), myeloma (16.9%), lung cancer (13.0%), breast cancer (7.9%) and other solid cancers.
The study, published in the Journal of Clinical Oncology [link here], found zoledronic acid was the most frequently prescribed bisphosphonate (81%), followed by pamidronate 60 mg (13%) and pamidronate 90 mg (6%).
The study found no statistically significant difference in serum calcium on day 4 based on the bisphosphonate chosen or the dose of pamidronate administered.
Median serum calcium on day 4 after bisphosphonate therapy was 9.0 mg/dL, 9.2 mg/dL, and 9.3 mg/dL for zoledronic acid 4 mg, pamidronate 60 mg, and pamidronate 90 mg, respectively.
There was however an increased incidence in hypocalcemia for patients who received zoledronic acid 4 mg compared with both pamidronate 60 mg and pamidronate 90 mg (40.7% v 27.6% and 26.8%; P = 0.049).
By day 7, normalisation of hypercalcemia was achieved/maintained in 32.8% patients, including 30% of patients who received zoledronic acid, 43% of patients who received pamidronate 60 mg, and 43% of patients who received pamidronate 90 mg.
Rates of hypocalcemia were similar across the groups at this time point.
By day 30, the median serum calcium levels were 9.1 mg/dL, 8.9 mg/dL, and 9.4 mg/dL for each bisphosphonate group.
“The incidence of hypocalcemia was 39%, 39%, and 38% respectively, with no difference when comparing zoledronic acid with pamidronate or when comparing different pamidronate doses,” the study said.
“Among those who were hypocalcemic at day 30, 31.6% required repletion with intravenous calcium; 30.6%, 25%, and 55.6% in the zoledronic acid 4 mg, pamidronate 60 mg, and pamidronate 90 mg groups, respectively.”
The study said bisphosphonate redosing and denosumab administration within 180 days after initial bisphosphonate treatment occurred in one in five patients (21.1%) and not significantly different between bisphosphonates or pamidronate dose groups.
Hospital length of stay was significantly longer for patients treated with pamidronate 60 mg versus zoledronic acid 4 mg (median 8 versus 6 days) but no different when comparing pamidronate 60 v 90 mg.
Hospital LOS was also significantly longer in patients who developed hypocalcemia at days 4 and 7 after bisphosphonate administration.
“This prolongation of hospital LOS can be associated with additional cost to the patient and to the health care system, including but not limited to additional supportive care needed, including specialty service consults, additional medications, and additional laboratory monitoring.”
Rates of readmission and death within 30 days of hospital discharge were similar between treatment groups.
The investigators said factors such as severity of baseline hypercalcemia and utilisation of concomitant treatments did not affect normalisation of calcium 30 days after bisphosphonate administration.
There was also no evidence of a dose-response relationship between pamidronate 60mg and 90mg doses.
“In summary, zoledronic acid 4 mg, pamidronate 60 mg, and pamidronate 90 mg are all safe and effective therapy for hypercalcemia of malignancy,” they concluded.