Download cancer associated hypercalcaemia

North West Coast Palliative and End of
Life Care Network
Audit Meeting
15/09/2016
Cancer Associated Hypercalcaemia
Guidelines for the Treatment of
Cancer Associated Hypercalcaemia
• Guideline Development Group:
Dr Amara Nwosu (Trainee lead)
Dr Melanie Brooks (Consultant lead)
Dr Jenny Smith (Consultant, lead of previous audit)
Dr Rachel McDonald (Trainee)
Dr Claire McKenzie (Doctor)
Alison White (Nurse)
Marie Keenan (Pharmacist)
Angela Fell (Lay representative)
With special thanks to……
• Invited Expert:
• Dr Allison Hall
Consultant Clinical Oncologist
Clatterbridge Cancer Centre
Patient & Carer involvement
• Representative = Angela Fell
– Involved throughout the entire audit process and
perspectives of issues pertinent to patients and families.
Standards and Guidelines
Current Guidelines
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Clinical assessment
Review current medications
Rehydration – saline
Bisphosphonates
Other drugs
Monitoring
Resistant and recurrent high calcium
Standards to be Audited
1. All patients with malignancy who have symptoms of
hypercalcaemia (see general principles) should have their
serum calcium measured if treatment is likely to be
appropriate [Grade D]
2. Patients with proven hypercalcaemia should receive
treatment within 24 hours if treatment is appropriate.
[Grade D]
3. All patients with cancer-associated hypercalcaemia should
be rehydrated with parenteral sodium chloride 0.9% prior
to treatment with bisphosphonates. [Grade D]
4. Serum calcium should be checked at 5-7 days. [Grade D]
5. Calcium levels should be rechecked every 3-4 weeks or
when symptoms of hypercalcaemia occur. [Grade D]
Literature review results
Hypercalcaemia Overview
• Common affects 8-40% of patients with cancer
• Three main mechanisms
i.
PTHrP related (80%)
i.
ii.
PTHrP similar to PTH (increased Ca release and increase Ca
reabsorption)
Direct metastatic invasion of bone
i.
Breast and myeloma
iii. <1%. Malignant cells recruit macrophages  1,25
dihydroxy vitamin D  increased calcium
Symptoms of Hypercalcaemia
Moderate:
• polyuria, thirst, nausea, vomiting, anorexia, fatigue,
constipation.
Severe:
• Confusion, arrhythmia, coma.
Treatment
• Treatment of dehydration
–
–
–
–
0.9% saline
Replace lost sodium
Increase glomerular filtration rate and circulating volume
Promote urinary calcium excretion
• Bisphosphonates:
– Analogues of pyrophosphate
– Reduce bone resorption by inhibiting osteoclasts
Question for the literature review
“What evidence exists in the literature about the
appropriate clinical management strategy of cancer
associated hypercalcaemia in adults?”
PICO
Participants
Cancer related hypercalcaemia in adults
palliative care
Any setting
Intervention
Therapeutic management of
hypercalcaemia (including fluids and
medications e.g. bisphosphonates and
denosamab
Comparator
-
Outcome
Symptoms
Survival
Hypocalacemia
Time to re-retreatment
Control
Alternative management
No treatment
Comparisons with other medications
Search strategy
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Medline
EMBASE
CINAHL
PsycInfo
Cochrane
NICE Evidence
Hand search (reference lists)
Search strategy
• Hypercalcaemia [MESH] OR Hypercalcemia
• AND (Neoplasm [MESH]OR Cancer OR Cancers OR neoplasms
OR tumor OR tomour OR malignant OR malignancy)
• AND "humans"[MeSH Terms] AND English[lang]) AND adults
>18 years
Exclusions
• Books
• Case reports, editorials, letters
• Articles not describing treatment of clinical hypercalcemia
• Review articles
• Paediatric populations
• Non-cancer
Medline
(n=77 )
CINALH
(n=141 )
PsycInfo
(n=0 )
EMBASE
(n=88 )
Total (n=313 )
Duplicates (n=12 )
Articles after duplicates
removed (n= 301)
Articles selected for
abstract after titles
screened
(n=81 )
Articles selected for
full text review
(n=40 )
Studies included in
the review (n=32)
Grey lit
(n=7)
Exclusions of abstracts (n=41)
Review = 20
No abstract = 11
Not describing treatment of
hypercalcaemia = 8
Case report = 2
Exclusions full text (n=8)
Duplicates =3
Unavailable =4
Not describing treatment of cancer
related hypercalcaemia =1
Literature review categories
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Preliminary bisphosphonate dose finding studies
Comparative bisphosphonates studies
Fluids
Calcitonin
Gallium
Steroids
Denosmab
Dose finding studies
Pamidronate
• Aminohydroxypropylidene (ADP)
• Oral (1200mg/day) vs IV (30mg/day) in 20 patients for 6 days normalises
Ca. (N=20) (Thiebaud 1986)
• Reduction in calcium with 30mg/2hr dose (N=16) (Cantwell 1987)
• Single dose of 1.0 – 1.5mg/kg as good as 3 day infusion (N=33) (Body
1989)
• Dose related response (higher doses = better Ca normalisation) (NeskovicKonstantnovic 1995 (N=34), Daragon 1991 (N=104))
• 70mg most efficacious dose (N=104) (Darragon 1991)
• No significant difference between 2 vs 4h and 8 vs 24 h infusions (N=50)
(Dodwell 1992)
• Progressively less effective when hypercalcaemia recurred. This was
observed mainly in patients without bone mets and without breast cancer
(N=29) (Body 2000).
Alendronate
• Doses >5mg significantly superior to 2.5mg dose. No
significant difference between 2hourly and 24hourly
treatment protocol (N=50). (Nussbaum 1993)
Clodronate
• No significant difference in response rates between varying
doses of clodronate (600 – 1500mg). Low dose equally
effective for mild hypercalcaemia as high dose for moderate
to severe (N=67) (Shah 2002).
• Subcutaneous clodronate (1500mg) safely given over 224hours. N=90 for high Ca. but missing data. Normalised Ca in
32/43 (74%) (Roemer-Becuwe 2003)
Etidronate
• Dose related response to treatment. 30mg/kg doses appears
safe. (N=30) (Flores 1994).
Ibandronate
• Dose dependent Ca reduction. 44%, 52% and 67% (for
0.6mg, 1.1mg and 2mg doses respectively). (N=151)
(Pecherstorfer 1996)
• No significant different between 4 and 6mg dose but signif
difference between 2mg dose and others: RR=
50%/75.6%/77.5% (N=131) (Ralston 1997)
• Higher PTHrP associated with higher tubular calcium
reabsorption. Higher levels seen with lung, kidney, urinary
and GI cancer. Relapse risk 3.43x for lung cancer & 2.23 for
kidney, urinary and digestive tracts. Ibandronate therapy
reduced PTHrP in 40% of breast cancers but only 26% of
lung cancers (N=321) (Rizzoli 1999)
Zoledronate
• 0.02mg/kg and 0.04mg/kg doses effective for hypercalcaemia
(N=30) (Body 1999)
• 84% response of hypercalcaemia within 10 days with
4mg/15min dose (N=27) (Kawada 2005)
Summary
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Mix of prospective and RCTs. Varying quality.
Small
Often not randomised
Determined efficacious dose of bisphosphonates
Illustrated common side effects (pyrexia, electrolytes
and renal impairment)
• Found dose dependent response applies
• Pamidronate (least potent)  zoledronic acid (most
potent)
Comparative bisphosphonate studies
Comparative Bisphosphonate Studies
• Pamidronate superior to Etidronate with a 70%
complete response rate compared to 41%
(Gulcap 1992)
• Zoledronic acid reported as superior to
Clodronate although significant issues with data
analysis (Sabry et al 2011)
• Zoledronic acid 4mg and 8mg superior to
Pamidronate 90mg – 88.4%, 86.7% and 69.7% of
respective treatment groups achieved complete
resolution 10 days post treatment in high quality
study (Major et al 2001)
Fluids
Fluids
• Intravenous saline alone inferior to intravenous
saline and Pamidronate 60mg – 78% complete
resolution compared to 22% (Gulcap et al 1994)
• Intravenous saline alone inferior to intravenous
saline and Clodronate – 81% complete resolution
compared to 21% (Rotstein et al 1992). Significant
methodological issues
Gallium
Gallium
• Inhibits calcium reabsorption from bone
• Has not been part of clinical practice in the UK
• However some international studies
– High quality study comparing Gallium with Pamidronate.
Gallium gave a superior complete response rate at 69%
compared with 56% (Cvitkovic et al 2006)
– Small study which showed Gallium to be superior to
Calcitonin (Warrell et al 1988)
– Reasonable quality study comparing Gallium with
Etidronate. Gallium gave a superior response rate at 82%
compared with 43% (Warrell et al 1991)
Steroids
Steroids
• No reduction of Ca observed with steroids (N=13)
(Thalassinos 1970)
• No different in Ca reduction in comparative study
‘fluids only’ vs. ‘fluids and prednisolone’ (N=28)
(Pervical 1987)
• Prednisolone, furosemide and rehydration superior
to furosemide and rehydration alone. RCT (N=30).
Methodological issues (Kristensen 1992)
Furosemide
Furosemide
• Subgroup analysis in several studies did not show any
benefit in patients given furosemide in addition to
fluids or fluids and bisphosphonates (Gulcap et al
1992 and Gulcap et al 1994)
• “No evidence to support the of furosemide use in
malignant hypercalcaemia”
• LeGrand SB, Leskuski D, Zama I. Narrative review:
furosemide for hypercalcemia: an unproven yet
common practice. Ann Intern Med 2008;149:259-63.
Denosumab
Denosumab
• High quality initial study by Hu et al 2014
– 33 patients with recurrent or resistant cancer associated
hypercalcaemia despite at least one prior treatment with
bisphosphonates.
– Patients given s/c Denosumab 120mg as per the dosing
protocol for prevention of SREs
– 79% were PS2 or less and estimated median survival after
study entry was 71 days
– 70% had a fall in calcium to 2.9 or less and 64% had a fall in
calcium to 2.7 or less
– Estimated median duration of response was 34 days at less
than 2.7 and 104 days at less than 2.9
Denosumab
• Of the 19 patients who reported symptoms possibly
related to hypercalcaemia 10 reported improvement
or resolution of at least 1 symptom
• Most common side effects were hypophosphataemia
and nausea
• Denosumab not metabolised or excreted by the
kidneys
• Small study with a short duration of follow up but
supports the use of Denosumab for treating resistant
and recurrent hypercalcaemia
Major findings
• Hydration used prior to bisphosphonates in most studies
• Bisphosphonates and fluids effective for hypercalcaemia
– Bisphosphonates and fluids are superior to fluids alone at least in moderate
and severe hypercalcaemia
• Evidence for use of gallium but requires longer infusions.
• Normalisation after treatment seen in 7 – 10 days in most studies.
• Evidence supports use of zoledronic acid as the bisphosphonate of choice
• Relapse rate after bisphosphonates median 3-4 weeks
• Fever highly prevalent side effect of bisphosphonates. Most studies report
– 30% of pts.
• Hypocalcaemia and hypomagnesia frequently seen after treatment
Major findings
• Higher risk of relapse and poor response for PTHrP driven tumours (lung
3x, kidney, urinary and digestive tracts 2x).
• No evidence for use of furosemide or steroids.
• No evidence for cinacalcet in malignancy.
• Denosumab is a possible therapeutic option in resistant or recurrent
hypercalcaemia.
New findings since previous audit
• Denosumab
• Local guidance advises fluids only if Ca
normalises after hydration.
Limitations of evidence
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Response by ethnicity?
Affect on symptoms and QoL?
Average number of hypercalcaemia episodes?
Limited data on relapse rate and clinical outcomes of
patients only receiving hydration
Role of subcutaneous fluids?
Long term outcomes of denosumab?
Management in community settings?
Ethical issues rarely addressed/considered.
Future research/study ideas
• What are the outcomes of a patients with cancer-related
hypercalcaemia receiving only parental fluids?
• How does treatment of cancer-related hypercalcaemia affect
on symptoms and quality of life?
• What is the role of denosumab in the management of cancerrelated hypercalcaemia?
• Do gallium nitrate, calcitonin and cinacalet have a role in
cancer-related hypercalcaemia?
Patient Mortality
• 5/77 patients (6%) died within 3 days of
diagnosis.
• Of these
• 2 were given fluids but no drug treatments as they
were felt to be dying
• 1 was given fluids but no drug treatments,
rationale unclear
• 2 had sodium chloride 0.9% and bisphosphonates
(Pamidronate 60mg and zoledronic acid 4mg)
Summary
No
STANDARD
ACHIEVED?
1
All patients with malignancy who have symptom of
hypercalcaemia (see general principles) should have their serum
calcium measured if treatment is likely to be appropriate
✔
2
Patients with proven hypercalcaemia should receive treatment
within 24 hours if treatment is appropriate
✔
3
All patients with cancer-associated hypercalcaemia should be
rehydrated with parenteral sodium chloride 0.9% prior to
treatment with bisphosphonates
✔
4
Serum calcium should be checked at 5-7 days
5
Calcium levels should be rechecked every 3-4 weeks or when
symptoms of hypercalcaemia occur
✖
✖
New Standards and Guidelines
Proposed Guidelines
22.1 GENERAL PRINCIPLES
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The normal range for the serum corrected calcium or albumin-adjusted calcium is 2.2-2.6mmol/l. 1
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Most laboratories now give corrected calcium results. An uncorrected calcium level may be adjusted for the serum albumin
using the following formula:
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Adjusted calcium (mmol/l) = Total calcium + 0.02(40-serum albumin).1
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Correction of calcium is especially important in patients with cancer who often have low albumin levels. The corrected
calcium is a better indicator of free physiologically active (ionised) calcium than the total calcium level in such patients. 1-8.
•
Hypercalcaemia is the commonest life-threatening metabolic disorder associated with malignancy, occurring in
approximately 10-20% of patients with cancer. It occurs primarily in those with more advanced disease and is generally
indicative of a poor prognosis. 1 -12 The incidence of cancer-associated hypercalcaemia is now falling because of earlier and
prolonged use of bisphosphonates in cancer patients with metastatic bone disease.3,8
•
In the past it was thought that tumour-associated hypercalcaemia only occurred in patients with bone metastases and
resulted from either the osteolytic process at the site of a bone metastasis or due to release from the tumour cells of
parathyroid hormone related protein (PTHrP) and possibly tumour growth factors. It is now known that most cases of
cancer-associated hypercalcaemia are due to the release of PTHrP from the underlying malignancy including in patients
without bone metastases. The diagnosis of hypercalcaemia should be considered in patients with cancer including those
who do not have bone metastases2,4,5,6,9-12 Symptoms of hypercalcaemia include: fatigue, weakness, constipation, nausea,
vomiting, polyuria, polydipsia, cardiac arrhythmias, delirium, drowsiness and coma. 1,2,4- 8,10,12 The severity of symptoms
correlates more closely with the rate of increase in calcium rather than the actual level. 2,4,6,7,8
•
Treatment of hypercalcaemia includes rehydration and the use of bisphosphonates. 1-8,10,11
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Hypercalcaemic patients are dehydrated and sodium depleted. Rehydration with parenteral
sodium chloride 0.9% should always be first line management. This may improve some of the
symptoms and may reduce calcium levels by 0.4-0.6mmol/l. 5 It has three main effects:
-
Replace lost sodium.
Increase the glomerular filtration rate and circulating volume.
Promote urinary calcium excretion. 2-6, 8,,10 11
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Sodium chloride 0.9% should be used in preference to dextrose as the reabsorption of
calcium in the proximal convoluted tubule is linked with that of sodium, hence saline
produces a more effective calcium diuresis.
•
Bisphosphonates are synthetic analogues of pyrophosphate and may be highly effective in
the treatment of hypercalcaemia of malignancy. 1,4,5,9-11 They inhibit bone resorption but have
no effect on renal tubular calcium reabsorption. 5
•
Until recently Disodium pamidronate was the initial bisphosphonate of choice standard
treatment for cancer-associated hypercalcaemia when they first became available. Zoledronic
acid is a newer aminobisphosphonate which is also licensed for the treatment of cancerassociated hypercalcaemia. Studies have shown it to be superior to pamidronate in terms of
a more rapid onset and a longer duration of action.9,11 and it has largely replaced
Pamidronate as the bisphosphonate of choice in managing cancer related hypercalcaemia.
Ibandronic acid is a third generation bisphosphonate which appears to have a better renal
profile.12,13 Local policies may govern which bisphosphonate is available for clinical use.
•
Side effects of bisphosphonates include a transient rise in body temperature, a flu-like syndrome,
renal toxicity, osteonecrosis of the jaw, asymptomatic hypocalcaemia and rarely ocular toxicity
(uveitis and scleritis) 9,11, 14-16
•
Denosumab is a human monoclonal antibody that binds to receptor activator of nuclear factor-B
ligand (RANKL) which is essential for differentiation, function and survival of osteoclasts. Denusomab
has high affinity and specificity for RANKL and by preventing it from binding to the RANK receptor on
osteoclasts it reduces osteoclast-mediated bone resorption. Hence it has a potential role in bone
diseases mediated by osteoclasts including metastatic bone disease18,19 and It has been shown in
randomised controlled trials to be more effective than zoledronic acid in preventing skeletal –related
events in patients with bone metastases from breast and prostate cancer and other solid tumours. 21
However its role in the management of cancer-associated hypercalcemia in palliative care patients is
currently uncertain and trials to clarify this are ongoing. 12,18 Recent small trials have shown
Denosumab to be effective in lowering corrected calcium levels in patients with hypercalcaemia that
has recurred after or is resistant to bisphosphonate treatment.
•
It is administered as a subcutaneous injection. Side-effects include osteonecrosis of the jaw,
dyspnoea, diarrhoea. 12,18 It does not cause renal toxicity. It is more expensive than bisphosphonate
therapy.19
22.2 GUIDELINES
• Clinical assessment of the patient is crucial in determining whether treatment of hypercalcaemia is
appropriate. Generally a decision to treat should be motivated by the patient`s symptomatology
rather than absolute calcium level. The most important goal of treatment is to improve clinical
symptoms. 2,3,5 [Level 4]
•
It may not be appropriate to treat cancer-related hypercalcaemia in a patient who is judged to be
imminently dying. If a decision not to treat cancer related hypercalcaemia is made this should be
clearly recorded in the case notes and communicated to the patient and/or those close to them
where this is possible.
22.2.1 Rehydration and discontinuation of other drugs
• The patient should be rehydrated with 1-3 litres of parenteral sodium chloride 0.9% over 24
to 48 hours before the administration of bisphosphonates. The volume and rate of fluid
replacement should be adjusted in each patient according to their age, the severity of
hypercalcaemia, the degree of dehydration and the ability of the cardiovascular system to
tolerate rehydration. 3, 5 [Level 4].
•
Drugs which reduce renal blood flow or renal calcium excretion should be
discontinued/avoided where appropriate e.g. non-steroidal anti-inflammatory agents and
thiazide diuretics. 3, 7 If a diuretic is needed, a loop diuretic such as furosemide, which inhibits
the reabsorption of calcium and sodium in the ascending limb of the loop of Henle, is the
drug of choice. 3, 5 However there is little evidence of benefit and diuretic use may exacerbate
hypovolaemia, hypokalaemia and hypomagnesaemia.12 [Level 4]
•
Some local clinical guidelines advocate initial parenteral rehydration and rechecking serum
calcium prior to further treatment. While rehydration will usually lower and in some cases
normalise serum calcium this response may be of short duration.
22.2.2 Bisphosphonates
• Please see Table 22.1 and Table 22.2 for details of the bisphosphonates available. Local
policies will govern which bisphosphonate is used.
Side effects of bisphosphonates
•
Renal toxicity has been associated with bisphosphonate treatment and may be manifested as
deterioration in renal function or renal failure. Monitoring of renal function is
recommended.3,6,8,10,11,14-16 Ibandronate has a better renal profile and may be the
bisphosphonate of choice for patients with moderate renal failure or if nephrotoxic medications
are being used concomitantly.12,13,16 If renal impairment is secondary to hypercalcemia renal
function may improve as the calcium level falls. 3,8
•
If symptomatic or severe hypocalcaemia occurs post bisphosphonate therapy, then short term
supplemental therapy may be required . Patients who have undergone thyroid or parathyroid
surgery may be particularly susceptible to developing hypocalcaemia due to relative
hypoparathyroidism.15 When bisphosphonates are administered with aminoglycosides and/or
loop diuretics caution is advised as both can lower calcium and magnesium levels for long
periods. 11, 14,15,16Level 4
•
In aspirin-sensitive patients treatment with bisphosphonates has been associated with
bronchospasm so caution is recommended in this group of patients. 11Level 4
•
Osteonecrosis of the jaw has been reported in patients receiving bisphosphonates.12,14- 16 (see
Guidelines on the Use of Bisphosphonates in Bone Pain).
•
Transient pyrexia has been reported in up to 30% of patients receiving bisphosphonates
22.2.3 Monitoring of hypercalcaemia
• Corrected calcium levels should be rechecked at 5-7 days after the bisphosphonate infusion.
Checking calcium levels prior to this is not appropriate, as the bisphosphonate will not have
achieved its maximal effect. 3,10, 15,16Level 4
• Corrected calcium levels should also be rechecked at 5-7 days following treatment of
hypercalcaemia with parenteral rehydration alone if further treatment of recurrent
hypercalcaemia would be appropriate. If calcium levels transiently normalised immediately after
rehydration many patients will have relapsed by this time.
•
Calcium levels should be rechecked every 3-4 weeks or when symptoms of hypercalcaemia occur. 1
[Level 4]
22.2.4 Management of treatment resistant hypercalcaemia
•
If at 5-7 days post bisphosphonate infusion, the corrected calcium level is greater than 3.0mmol/l
or the patients' symptoms of hypercalcaemia persist, it may be appropriate to consider further
infusions of bisphosphonates. At least 7 days should elapse before a further treatment is given, to
allow maximal response to the initial dose. Options for treatment include: the same dose of
bisphosphonate; an increased dose or changing to an alternative bisphosphonate. 3,10, 11,15,16 [Level
4]
22.2.5 Management of recurrent hypercalcaemia
• If the patient experiences subsequent episodes of symptomatic hypercalcaemia, a further
infusion of bisphosphonate may be given. Depending on how close the recurrence is to the
original episode, it may be appropriate to give the same dose of bisphosphonate, an increased
dose or change to an alternative bisphosphonate. 10, 11,15, 16[Level 4]
•
•
Relapsing hypercalcemia usually does not respond as well to bisphosphonate as well as the
initial episode.4,9,15 Level 4
If recurrent or resistant hypercalcaemia fails to respond to re-treatment with bisphosphonates
Denosumab should be considered as an alternative treatment if it is locally available.
22.3 ROLE OF OTHER AGENTS AVAILABLE IN THE TREATMENT OF CANCER-ASSOCIATED
HYPERCALCAEMIA
22.3.1 Calcitonin (Salcatonin)
• Calcitonin should only be used in exceptional circumstances when the corrected calcium level
is extremely high and there is a clinical indication for the rapid reduction of the serum calcium
level eg in the event of symptomatic cardiac arrhythmias.2,5,8,10 [Level 3].
• It should be given in addition to the bisphosphonate. Calcitonin reduces the calcium level
rapidly whilst the slower acting bisphosphonate will take longer to work but achieve a more
long lasting effect.4,5,12,17 Level 3
• The dose range is from 100IU international units every 6- 8 hours to a maximum of 400IU
international units qds. It can be administered as an injection subcutaneously, or
intramuscularly. 8,12,17 [Level 3]
• Calcitonin is highly emetogenic, nausea with or without vomiting occurring in approximately
10% of patients treated with calcitonin 4,17 and should be co-prescribed with an antiemetic
such as haloperidol. [Level 4].
• Other common side effects of calcitonin include rash and flushing. 2,4,12,17 [Level 4]
22.3.2 Corticosteroids
•
The role of steroids in severe hypercalcaemia is confined to haematological tumours that
respond to the cytostatic effects of steroids including myeloma,leukaemia and lymphoma. 1,3,5
Level 4
22.3.3 Gallium Nitrate
• This has been shown in several non-UK based studies to have comparable efficacy to
bisphosphonates in treating cancer related hypercalcaemia. However it requires a continuous
intravenous infusion over several days to administer and is not used in clinical practice in the
UK.
New proposed standards
•
All patients with malignancy who have symptom of hypercalcaemia (see general principles)
should have their serum calcium measured if treatment is likely to be appropriate [Grade D]1
•
Patients with proven hypercalcaemia should receive treatment within 24 hours if treatment is
appropriate. 2, 5 [Grade D]
•
When hydrating patients with cancer-associated hypercalcaemia intravenous 0.9% saline
should be used.
•
All patients being treated with bisphosphonates for cancer-associated hypercalcaemia should
receive intravenous fluids prior to treatment. 2, 3, 4, 10, 11 [Grade D]
•
Following any treatment of hypercalcaemia (including with intravenous fluids alone) the
serum calcium should be rechecked after 5-7 days.
•
Calcium levels should be rechecked every 3-4 weeks, following the completion of
hypercalcaemia treatment, or when symptoms of hypercalcaemia occur.
•
Denosomab should be considered for the management of resistant or recurrent
hypercalcaemia of malignancy where repeated treatment with bisphosphonates fails to
normalise the serum calcium.
Patient and public
representative
Invited Expert
Thank you for Listening
Any Questions?