Anti-tumor treatment for sudden hypercalcemia? The guide teaches you how to deal with it!

*For medical professionals only

Forward to learn!

Written by | Lily

Hypercalcaemia (HCM) is the most common metabolic complication
in patients with malignancy.
HCM is estimated to affect 2% to 30% of cancer patients, most commonly in breast, lung, kidney and multiple myeloma
.
Although earlier studies reported up to 50% 30-day mortality in HCM patients, this has improved significantly over the past few decades
, largely due to more effective anti-tumor and supportive care.

Recently, the Journal of Clinical Endocrinology and Metabolism (JCEM) released the first "Treatment of hypercalcemia in adult malignancies: a clinical practice guideline of the Endocrine Society"
.
The guidelines provide clinical diagnosis and treatment according to the severity and pathophysiology of HCM, and the medical oncology channel focuses on the following:

Figure 1.
Screenshot of the first page of the guide

1.
Guidance on the use of relevant drugs and a general diagram of HCM diagnosis and treatment process

In the US, the estimated median length of hospital stay associated with HCM admission is 4 days, and the in-hospital mortality rate is 6.
8%.

This short average hospital stay compared to historical values reflects the prevalence of strong anti-bone resorptive drugs for HCM and its comorbidities
in a series of recent studies (30-40%).
Timely and effective control of HCM treatment is a key factor
in reducing morbidity and length of hospital stay.

The doses, onset of action, and frequency of use discussed in this guideline are detailed in Table 1
.

Table 1.
Treatment options
for HCM.

Abbreviations: HCM, hypercalcemia of malignant tumor; ONJ, osteonecrosis of the jaw; RANK, nuclear factor kappa-B receptor activator; RANKL, a receptor activator
of the nuclear factor kappa-B ligand.

*Loop diuretics
should not be routinely used.
However, in patients with renal insufficiency or heart failure, loop diuretics may need to be used wisely to prevent fluid overload
during saline hydration.

Treatment of HCM depends on the pathophysiology and severity of hypercalcaemia and the rate at
which serum calcium rises.
Hypercalcemia was divided into mild, serum albumin-corrected calcium< 12 mg/dL (normal<3 mmol/L) according to severity; Moderate, serum albumin-corrected serum calcium 12-14 mg/dL (normal 3-3.
5 mmol/L; Severe, serum albumin-corrected blood calcium > 14mg/dL; (Normal value> 3.
5mmol/L).

The diagnosis and treatment process of HCM is shown in Figure 2
.

Figure 2.
HCM treatment flow chart
.
Abbreviations: IV BP, intravenous bisphosphonate; DMAB, denosumab; PTH parathyroid glands

2.
Specific recommendations

1.
Adult malignant tumor hypercalcemia

Q1.
Should adult patients with HCM be treated with bisphosphonates or denosumab?

Recommendation 1.
For adult patients with HCM, intravenous bisphosphonates or denosumab
are recommended compared with treatment without intravenous bisphosphonates or denosumab.

Q2.
Should denosumab and bisphosphonates be used in adult patients with HCM?

Recommendation 2.
For adult patients with HCM, denosumab is recommended instead of intravenous bisphosphonate
.

Q3.
Should calcitonin be added to adult patients with severe HCM who will be started on bisphosphonates or denosumab?

Recommendation 3.
For adults with severe HCM [serum calcium>14 mg/dL (3.
5 mmol/L)], calcitonin plus intravenous bisphosphonate or denosumab is recommended as initial therapy
compared with intravenous bisphosphonates or denosumab alone.

Remark:

•Calcitonin therapy should be limited to 48 to 72 hours
due to rapid tolerance.

2.
Refractory and recurrent hypercalcemia

Q4.
Is denosumab suitable for adult patients with bisphosphonate-refractory/recurrent HCM?

Recommendation 4: For adult patients with intravenous bisphosphonate refractory/recurrent HCM, denosumab is recommended compared with treatment without denosumab
.

3.
Hypercalcemia caused by calcitriol-related malignancies

Q5.
Should bisphosphonates or denosumab be used in patients with hypercalcemia due to hypercalcitriol-associated tumors that have been treated with glucocorticoids?

Recommendation 5.
For adults with severe or symptomatic HCM who have been treated with glucocorticoids, it is recommended to add intravenous bisphosphonates or denosumab
to treatment without intravenous bisphosphonates or denosumab.

4.
Hypercalcemia caused by parathyroid (PTH) carcinoma

Q6.
Should adult patients with hypercalcemia due to parathyroid carcinoma be treated with calcimimetic, bisphosphonates or denosumab?

Recommendation 6.
For adult patients with hypercalcemia due to parathyroid carcinoma, treatment with calcimimetic or intravenous bisphosphonates or denosumab is recommended
.

Remark:

•In adult patients with parathyroid carcinoma, surgery should be considered once severe HCM is under control; However, surgical considerations are outside the scope of
this guideline.

•Depending on the clinical situation and severity of hypercalcaemia, intravenous bisphosphonates or denosumab may be effective
prior to the initiation of calcimimetic.
For adult patients with mild HCM and related symptoms, it is recommended to start treatment with calcimimetic; Conversely, intravenous bisphosphonates or denosumab should be initial therapy
in adults with moderate to severe HCM and associated symptoms.

•This guideline takes into account that intravenous bisphosphonates or denosumab have a faster onset of action and are generally better tolerated than calcimimetic (adverse events are common as calcimimetic doses increase).

Q7.
For adult patients with hypercalcemia due to parathyroid adenocarcinoma with poorly controlled calcimimetic, should intravenous bisphosphonate or denosumab be added to intravenous bisphosphonate or denosumab?

Recommendation 7.
For adult patients with hypercalcemia due to parathyroid carcinoma, when it is not adequately controlled despite calcimimetic therapy, it is recommended to add intravenous bisphosphonate or denosumab compared with no intravenous bisphosphonate or denosumab
.

Q8.
Should calcimimetic be used in adult patients with hypercalcemia due to parathyroid carcinoma that cannot be adequately controlled by bisphosphonates or denosumab compared to calcimimetic?

Recommendation 8.
For adult patients with hypercalcaemia due to parathyroid carcinoma, if intravenous bisphosphonate or denosumab therapy is not adequately controlled, it is recommended to add calcimimetic
compared with treatment without calcimimetic.

References:

Reviewed: Xu Weiran

Editor-in-charge: Sweet

*This article is only used to provide scientific information to medical professionals and does not represent the views of this platform