London-Cancer-Guidelines-managemen-of-skeletal-events-updated-v1

Version: 1
Based on the Barts Health Guideline written by: Chris Watson and Checked by Sarah Slater
Reviewed and Updated by Simon Jenkinson
Page 1 of 17
Version dated: February 2014
Review date: February 2016
Guideline for the Management of Skeletal Related Events
1.
Treatment/Prevention of Skeletal Events related to Metastatic
Disease
Page 2
2.
Prevention of Osteoporotic Fractures in Cancer Patients
Page 3
3.
Treatment Algorithm for Management of SRE’s
Page 4
4.
Specific Drug Information and Adverse Effects
Page 6
o Denosumab
Page 7
o Zoledronic Acid
Page 8
o Pamidronate
Page 8
5.
Appendices
o Appendix A: Blood Tests
Page 9
o Appendix B: Referral Proforma letters and Forms
for dental referral
Page 10

Version: 1
Based on the Barts Health Guideline written by: Chris Watson and Checked by Sarah Slater
Reviewed and Updated by Simon Jenkinson
Page 2 of 17
Version dated: February 2014
Review date: February 2016
Treatment/Prevention of Skeletal Events related to Metastatic
Disease
 First line: Denosumab (XGEVA®) 120mg S/C except prostate and multiple
myeloma patients- given every 4 weeks only*
This is indicated for patients with bone metastasis due to breast cancer/other solid
tumours except prostate tumours and multiple myeloma.
NICE TA268 (October 2012)
Denosumab is recommended as an option for preventing skeletal-related events (pathological fracture, radiation to bone, spinal
cord compression or surgery to bone) in adults with bone metastases from breast cancer and from solid tumours other than
prostate if:
o bisphosphonates would otherwise be prescribed AND
o the manufacturer provides denosumab with the discount agreed in the patient access scheme.
Denosumab is not recommended for preventing skeletal-related events in adults with bone metastases from prostate cancer.
Patients receiving denosumab should be prescribed 500mg calcium and 400iu Vitamin D
supplements e.g. Adcal D3 tablets, one to be chewed daily.
 Patients with prostate cancer or multiple myeloma should receive Zoledronic acid 4mg IV
first line every 3 or 4 weeks instead of denosumab. If the patient has CrCl <29ml/min then
Pamidronate 90mg should be prescribed every 3 or 4 weeks- see guidance in section f
regarding administration
*Zoledronic Acid 4mg IV every 3 or 4 weeks first line can be used for providers who
are unable to implement NICE TA268
 Second line: Zoledronic Acid 4mg IV (dose adjusted to renal function) every 3 or
4 weeks
This is indicated for patients who cannot tolerate denosumab or are hypersensitive to it.
Patients receiving zoledronic acid should be prescribed 500mg calcium and 400iu Vitamin D
supplements e.g. Adcal D3 tablets, one to be chewed daily.
If the patient has CrCl <29ml/min then Pamidronate 90mg should be prescribed every 3 or
4 weeks- see guidance in section f regarding administration.

Version: 1
Based on the Barts Health Guideline written by: Chris Watson and Checked by Sarah Slater
Reviewed and Updated by Simon Jenkinson
Page 3 of 17
Version dated: February 2014
Review date: February 2016
Breast Cancer Treatment Induced Bone Loss
 Zoledronic Acid 4mg IV (dose adjusted to renal function) every 6 months.
Approved for two groups of patients:
1. Breast Cancer patients for treatment-induced bone loss in women who experience
premature menopause due to chemotherapy or has ovarian suppression, ablation or
removal.
2. Breast cancer postmenopausal patient receiving treatment with aromatase inhibitors.
In both groups of patients one of the conditions below MUST apply:
o There is failure to achieve the required response on oral bisphosphonates.
o Oral bisphosphonates are not tolerated at the optimal dose
o The patient with oesophageal disease where oral bisphosphonates are contra-
indicated but intravenous bisphosphonates are considered appropriate.
Please refer to Breast Cancer Treatment guidelines for further guidance regarding Assessment of
Bone Health with Endocrine Treatment.

Version: 1
Based on the Barts Health Guideline written by: Chris Watson and Checked by Sarah Slater
Reviewed and Updated by Simon Jenkinson
Page 4 of 17
Version dated: February 2014
Review date: February 2016
Does the patient have severe untreated hypocalcaemia or
hypercalcaemia of malignancy?
1st Line: Denosumab 120mg SC 4 weekly &
Calcium supplement
2nd Line (if cannot tolerate denosumab:
Zoledronic Acid 4mg IV 3 or 4 weekly &
Calcium supplement or pamidronate if
<29ml/min
Correct hypocalcaemia or treat the
hypercalcaemia of malignancy
(Refer to Hypocalcaemia guidelines or
Guidelines for the treatment of Hypercalcaemia
of Malignancy)
Does the patient have:
o prostate cancer
o multiple myeloma
o Breast Cancer Treatment Induced Bone loss?
NO
YES
NO
1st Line: Denosumab 120mg SC 4 weekly & Adcal D3
ONE tablet daily
2nd Line (if cannot tolerate denosumab: Zoledronic
Acid 4mg IV 3 or 4 weekly & Calcium supplement
daily) or pamidronate if CrCl<29ml/min
New cancer patient requiring treatment for skeletal related events
For Prostate and Multiple Myeloma Patients:
o Zoledronic acid 4mg IV 3 or 4 weekly
(Frequency of zoledronic acid depends on
frequency of concurrent chemotherapy)
For Breast Cancer Treatment induced bone
loss**:
o Zoledronic Acid 4mg IV 6 monthly
YES
**Breast Cancer patients for treatment-induced bone loss in women who
experience premature menopause due to chemotherapy or has ovarian
suppression, ablation or removal.
OR
Breast cancer postmenopausal patient receiving treatment with aromatase
inhibitors.
Where there is failure to achieve the required response on oral
bisphosphonates. Where oral bisphosphonates are not tolerated at the
optimal dose. In patients with oesophageal disease where oral
bisphosphonates are contra-indicated but intravenous bisphosphonates
are considered appropriate.
3. Treatment Algorithm for Management SRE

Version: 1
Based on the Barts Health Guideline written by: Chris Watson and Checked by Sarah Slater
Reviewed and Updated by Simon Jenkinson
Page 5 of 17
Version dated: February 2014
Review date: February 2016
Specific Drug Information and Adverse Effects
a. Osteonecrosis of the Jaw
All oncology/haematology patients starting Denosumab or bisphosphonate therapy should
be informed about the rare but serious risk of developing osteonecrosis of the jaw.
The patient's dentist practitioner should be made aware of the intention to commence
Denosumab/bisphosphonate treatment and asked to perform a dental examination prior to
the first dose being administered.
See referral forms and algorithm in the appendices. Please note the multiple myeloma
patients pathway with dental assessment/Maxillo-Facial surgery review is yet to be
determined. Please contact Dr Jamie Cavenagh.
Once treatment has started, patients should receive 6 monthly dental reviews and avoid
invasive dental procedures if at all possible.
b. Symptom Control of flu-like Syndrome with IV Bisphosphonates
Paracetamol can be recommended for symptom control of flu-like syndrome, fever, myalgia
or arthralgia. These symptoms tend to occur with the first two doses, and then are less likely
to occur with subsequent treatment.
c. Femoral Fractures
Femoral fractures have been reported with bisphosphonate/denosumab therapy, primarily in
patients receiving long-term treatment for osteoporosis.
These transverse or short oblique fractures can occur anywhere along the femur from just
below the lesser trochanter to just above the supracondylar flare.
These fractures occur after minimal or no trauma and some patients experience thigh or
groin pain, often associated with imaging features of stress fractures, weeks to months
before presenting with a completed femoral fracture.
Fractures are often bilateral; therefore the contralateral femur should be examined in
bisphosphonate/denosumab-treated patients who have sustained a femoral shaft fracture.