Persistent Hypercalcemia of Malignancy - Novel Therapeutic

Strategy

Dr Sudhir Ranjan DashDr Vishal Ramteke

Case summaryMrs VDA56 yrs , Female

k/c/o Metastatic adenocarcinoma right breast(lung , liver, peritoneal,omental mets) diagnosed in Oct - 2012

Undergone Modified Radical Mastectomy + Chemotherapy (Paclitaxel,Eribulin,Cisplastin based)

Admitted under oncology services in Dec 2013 with –• Drowsiness • Poor oral intake

On evaluation – no focal neurodeficit noted Neuroimaging ruled out cerebral mets.

• Serum Calcium - 13.9 mg/dl, • Serum Albumin – 1.8 gm%, • Albumin Corrected Calcium- 15.8 mg/dl

Her previous admissions in JHRC on multiple occasions were marked by hypercalcemia which were managed each time by oncology team with Zolendronic AcidCalcitonin

Nephrology consultation was sought on this admission for management of hypercalcemia refractory to Zolendronic acid.

Normal Saline+ Lasix Dexamethasone

4/3/2013 7/11/2013 4/12/2013 14/12/13

Sr.Calcium 14.2 17.2 11.2 13.9ACC- 15.8

Ionised Ca 7.9 9.7 6.6 8.0

PTH 52.4 38.2 ------ 34.4

Vit D3 64.9 49.3 ------ 42.4

Total Protein

6.4 5.4 5.2 5.0

Albumin 2.9 2.1 2.0 1.8

FIRST CONSULTATION ↑

• The cause for the hypercalcemia was attributed to Humoral (PTHrP related ) Hypercalcemia of Malignancy.

• Since patient had received zolendronic acid 10 days back, it was not repeated in this admission.

• Other measures (saline diuresis, calcitonin, dexamethasone) were tried.

• She was started on tab Cinacalcet 30 mg Q12H .

• In/v/o hypercalcemia not responding to above measures administration of inj. DENOSUMAB was planned.

Denosumab is a fully human monoclonal IgG2 antibody that selectively binds to RANK ligand (RANKL) inhibiting the osteoclast – “Development, Activation and Survival”

It thus reduces osteoclast mediated bone resorption

Hypercalcemia due to bone resorption

DENOSUMAB

Inj Denosumab 120 mg s.c was given on day 1, day 8, day 15, day 29 and 60

DAY 0 DAY 3 DAY 7 DAY 30 DAY 60 DAY 90

T.Cal 13.9 12.1 10.8 10.2 9.1 7.7

i.Cal 8 6.9 6.0 5.3 5.1 4.8

0 3 7 30 60 900

2

4

6

8

10

12

14

16Total calcium

DAYS

Denosumab was approved by US FDA in 2010 for• Osteoporosis in post menopausal women• Prevention of skeleton-related events (SRE) in

patients with bone metastasis from solid tumors

• Off label use for hypercalcemia of malignancy have been tried recently

“Denosumab for patients with persistent or relapsed hypercalcemia of malignancy despite recent Bisphosphonate treatment”

Mimi I. Hu et al.J Natl Cancer Inst; July 2013;105:1417–1420

• 15 patients(hematologic malignancies, solid organ tumor)• Albumin corrected serum calcium > 12.5 mg/dl • Who have received inj Zolendronic acid within 7-30 days• Were given Inj Denosumab 120 mg on day 1, 8, 15 and 29 followed by every 4 week.

• By day 10 – 12 patients (80%) responded to achieve Albumin

corrected serum Calcium i.e. (ACSC) ≤11.5 mg/dL 10 patients (67%) had complete responses (ACSC) ≤10.8 mg/dL

• Median response duration for all patients was 26 days.

• Requires no renal dose adjustment• Hypocalcemia , hypophosphatemia, osteonecrosis of

jaw may be noted.• Hypersensitivity reactions may be seen• Cost – 120 mg cost 28,000 INR

THANK YOU