Bone Modifying Agents and Hypercalcemia Flashcards
Epidemiology
20 – 30% of all cancer patients
– decreased due to increased ___ use
Most common tumor types
– Lung – 35%
– Breast – 25%
– Hematologic – 14%
– Genitourinary – 6%
bisphosphonate
Pathophysiology of HCM
- ___ parathyroid hormone related protein (PTHrP)
- ___ calcitriol
- ___ resorption
- ___ elimination
- Bone metastases
increased
increased
increased
decreased
HCM Etiology
- Humoral (80% of cases)
- Local osteolytic hypercalcemia
(20% of cases) Caused by cytokines and PTHrP - 1, 25(OH)2D-Secreting Lymphomas
- . Ectopic hyperparathyroidism
- Renal (increased ___ reabsorption, Decreased ___ reabsorption)
- calcium
- phosphorus
Corrected Calcium
Serum Calcium + 0.8 (4 – Serum Albumin)
Normal Calcium: 8.5-10 mg/dL
Mild HCM (10-12 mg/dL)
Asymptomatic or mild symptoms
- Encourage hydration
- Discontinue medications that increase serum calcium or decrease renal blood flow
- Repeat calcium level in 4 weeks
Moderate symptoms
– Hydration: 200 - 400 mL/Hr of 0.9% normal saline
– Bisphosphonate: ___ or ___
* Can be repeated after 7 days if needed
Zoledronic acid or Pamidronate
Moderate HCM (12 – 14 mg/dL)
T or F: hydration reduces calcium more quickly than a bisphosphonate and Loop diuretics should be reserved for patients who develop fluid overload
T
Moderate HCM (12 – 14 mg/dL)
Bisphosphonate
- ___ Acid
- superior to pamidronate for treatment of moderate to severe hypercalcemia
Zoledronic
Severe HCM (> 14 mg/dL)
Hydration, Hydration, Hydration!!
– Typically, ___ mL/Hr
Bisphosphonates
Calcitonin
- ___ after 48 hours
- Hypersensitivity reactions, arthralgias, flushing, or nausea
200
Tachyphylaxis
FDA approved
refractory HCM
Denosumab
Chronic HCM Management
___ and ___
zoledronic acid, pamidronate
Comparison of Agents
NS and bisphosphonates = mild + severe
loop diuretics = moderate + severe
calcitonin = severe
Intravenous Bisphosphonates
Affinity for ___
Inhibit osteoclast activity through:
- Induce direct osteoclast apoptosis
- Inhibit differentiation and maturation
- Decreasing bone ___
- Increasing mineralization
- Concentrate at active bone remodeling sites
hydroxyapatite
resorption
Bone in Cancer Patients
Tumor cells secrete cytokines and growth factor
* increased production of receptor activate or nuclear factor kappa B
ligand ( ___ )
* increased osteoclasts lead to more bone ___
RANK-L
resorption
Epidemiology of Bone Metastases
Cancers with affinity for bone
* ___
* ___
* Myeloma
* ___
* Kidney
- Usually metastasizes to the ___ skeleton
- breast
- prostate
- lung
- axial
Skeletal Related Events (SRE’s)
Defined as:
1. Pathologic fracture
2. Need for bone radiation
3. Need for bone surgery
4. Spinal cord ___
5. Hyper ___
s/s
- Bony pain or tenderness
Radionucleotide bone scan > radiograph
compression
hypercalcemia
Risk Factors for Fractures
Women: Breast Cancer
* Bone mineral density < -2.5
* On aromatase inhibitors
* Age > 65
- ___ use > 6 months
* BMI < 20 kg/m 2
* Family history of hip fractures
* History of fracture before age of 50
* Smoking
Men with Prostate
Cancer
* Androgen deprivation
therapy
* Smoking
Treatment of Bone Metastases
Goal: Palliation of
symptoms
* Radiation
* Chemotherapy
* IV bone modifying
agents
– Delays time to first
SRE by 50%
* Radioisotopes
Radiation Therapy
* Overall response rates of 85%
* Pain relief within 1 to 2 weeks
– If pain relief not achieved by 6 weeks, unlikely
to see benefit
– No difference between single and multiple
fractions
– Limited by life-time limits of radiation within
certain areas
Radioisotopes
- Delivered more specifically to the tumor
- Treatment of bone metastases from thyroid cancer with 131-Iodine
- Radium-223 chloride shown overall survival benefits in ___ cancer
- Strontium and samarium used in metastatic breast and prostate cancers
- Expensive and have toxicities ( ___ )
prostate
myelosuppression
T or F: no renal adjustments are warranted if these agents (zoledronic acid and pamidronate) are for HCM
T
V Bisphosphonates for SRE’s
___ :90 mg IV over 2 hours every 3 to 4 weeks
– Renal adjustment dosing needed
___ acid : 4 mg IV over 15 minutes every 3 to 4 weeks or every 12 weeks
– Renal adjustment dosing needed
pamidronate
zoledronic
Bisphosphonates
– Supplement with ___ and ___
calcium
vitamin D
Denosumab
Fully human monoclonal antibody with high affinity for ___
- Rapidly reduces bone turnover
- Lack of affinity for hydroxyapatite and more evenly spreads throughout bone
- May suppress residual ___ function in patients who poorly responds to bisphosphonates
Bone metastases from solid tumors - ___
For women at high risk of fracture and
receiving aromatase inhibitors for breast cancer and in men receiving androgen deprivation therapy for prostate cancer – ___
- RANK-L
- osteoclast
- Xgeva
- Prolia
Denosumab Considerations
- Correct ___ prior to initiation
- Supplement calcium and Vitamin D daily
- NO renal dose adjustments
hypocalcemia
Adverse Effects of Therapies
Osteonecrosis of ___
- Angiogenesis suppression
- Osteocyte depletion leading to avascular necrosis
Possible treatment options:
– Palliative, pain control, chlorhexidine and/or antibiotics, conservative surgeries
Agent discontinuation may be associated with slow improvement but may not return to normal
jaw
Renal Dysfunction in this Setting
Zoledronic acid > pamidronate > denosumab
Bisphosphonate
- Not recommended for CrCl < ___ mL/min
Denosumab
- Not renally eliminated
- No renal or hepatic dosing adjustments
- No specific dosing recommendations for those on dialysis
30
Other Adverse Effects
Hypocalcemia:
- ___»_space; zoledronic acid
- Patients should be supplemented with daily calcium and vitamin D when using for prevention of SRE’s
* Bone pain
* Nausea
* Diarrhea
* Fatigue
Denosumab
Duration of Treatment
In clinical practice, typically will use every ___
month dosing
3
