Genitourinary - Renal Cell / Kidney
Lung - Mesothelioma
Lung - Non-Small Cell
Lung - Small Cell
Lung - Thymoma
Regimen is considered appropriate as part of the standard care of patients; meaningfully improves outcomes (survival, quality of life), tolerability or costs compared to alternatives (recommended by the Disease Site Team and national consensus body e.g. pan-Canadian Oncology Drug Review, pCODR). Recommendation is based on an appropriately conducted phase III clinical trial relevant to the Canadian context OR (where phase III trials are not feasible) an appropriately sized phase II trial. Regimens where one or more drugs are not approved by Health Canada for any indication will be identified under Rationale and Use.
For reducing the risk of developing skeletal-related events in patients with bone metastases.
|denosumab||120 mg||SC||Day 1|
|(This drug is not currently publicly funded for this regimen and intent)|
Other Supportive Care:
All patients, except those with hypercalcemia, should receive the following supplementation:
- at least 500mg of calcium daily
- at least 400 IU of vitamin D daily
Doses should be modified according to the protocol by which the patient is being treated. The following recommendations have been adapted from clinical trials or product monographs and could be considered.
Pre-existing hypocalcemia must be corrected prior to starting treatment.
Patients being treated with denosumab should not be treated concomitantly with bisphosphonates.
Dosage with toxicity
|Grade 3 or 4 drug-related toxicity||Consider holding or discontinuing|
|Osteonecrosis of the jaw||Follow guidelines for management. Consider holding or discontinuing treatment. Refer patient to dentist or oral surgeon.|
|Hypocalcemia||Treat appropriately. Consider holding or discontinuing treatment if severe.|
|Anaphylaxis or significant hypersensitivity||Treat appropriately. Discontinue denosumab permanently.|
No studies have been conducted in patients with hepatic impairment.
No dose adjustment is required with renal impairment. Patients with renal impairment are at increased risk of severe life threatening hypocalcemia and require increased monitoring (refer to monitoring section).
Dosage in the Elderly
No adjustment required. No overall differences in safety and efficacy.
May impair bone growth and tooth eruption in pediatric patients. Safety and efficacy have not been established and therefore not indicated in pediatric patients, except in skeletally mature adolescents (aged 13-17 years) with giant cell tumour of bone. Severe hypercalcemia has been reported in patients with growing skeletons, weeks to months following denosumab discontinuation
Refer to denosumab drug monograph(s) for additional details of adverse effects
Less common (10-24%)
Uncommon (< 10%),
but may be severe or life-threatening
Refer to denosumab drug monograph(s) for additional details
- Exercise caution when given with drugs that may cause hypocalcemia. Monitor calcium levels closely.
Refer to denosumab drug monograph(s) for additional details
- Inject subcutaneously in the upper arm, upper thigh, or the abdomen.
- Should not be administered intravenously, intramuscularly or intradermally
- Use a 27-gauge needle to withdraw or inject the drug. Avoid vigorous shaking of the drug.
- Denosumab should appear clear, colourless to slightly yellow. It may contain trace amounts of translucent or white proteinaceous particles. Do not use if the solution is discoloured, cloudy, contains many particles or foreign matter.
- If a dose is missed, it may be given as soon as possible and the subsequent injection should be scheduled q4 weeks from the most recent injection date.
- Keep refrigerated in the original carton between 2-8°C. Protect from direct light
- Before use, the drug vial (in its original container) can be brought to room temperature (usually takes 15-30 minutes). Do not warm the drug by other methods. Once removed from the refrigerator, it must be stored at room temperature (≤ 25°C) and used within 30 days.
- Contraindicated in patients who have a hypersensitivity to this drug or any of its components
- Do not use Xgeva® with Prolia®, as both products contain the same active ingredient, denosumab.
- Patients being treated with denosumab should not be treated concomitantly with bisphosphonates
- Pre-existing hypocalcemia must be corrected before starting denosumab treatment. Risk of hypocalcemia is greater in patients with moderate to severe renal impairment. Patients, except those with hypercalcemia, should receive adequate calcium and vitamin D supplementation (see Dosing section).
- Risk-benefit should be assessed for patients with risk factors for ONJ before starting treatment.
Pregnancy and Lactation:
- Denosumab is not recommended for use in pregnancy. Adequate contraception should be used by both sexes during treatment, at for at least 5 months after the last denosumab dose. Women who become pregnant during denosumab treatment are encouraged to enroll in the manufacturer's Pregnancy Surveillance Program.
- Lactation: Not recommended. Women who are nursing during denosumab treatment are encouraged to enroll in the manufacturer’s Lactation Surveillance Program.
- Fertility effects: Unlikely
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
Recommended Clinical Monitoring
- Calcium, phosphate, magnesium - No hypercalcemia: baseline, within 2 weeks of the first dose, and as clinically indicated. In hypercalcemia: baseline, before each dose and as clinically indicated. Additional monitoring with renal dysfunction, symptoms of hypercalcemia and in patients with growing skeleton.
- Dental examination with appropriate preventative dentistry should be considered prior to treatment. Regular dental check-ups. Avoid invasive dental surgeries while on treatment.
- Vertebral fractures; evaluate patient risk after treatment discontinuation
- Clinical toxicity assessment for fatigue, musculoskeletal effects, hypocalcemia, ONJ, cough/dyspnea; at each visit
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
Denosumab drug monograph, Cancer Care Ontario.
Henry DH, Costa L, Goldwasser F, et al. Randomized, double-blind study of denosumab versus zoledronic acid in the treatment of bone metastases in patients with advanced cancer (excluding breast and prostate cancer) or multiple myeloma. J Clin Oncol 2011;29(9):1125-32.
Stopeck AT, Lipton A, Body JJ, et al. Denosumab Compared With Zoledronic Acid for the Treatment of Bone Metastases in Patients With Advanced Breast Cancer: A Randomized, Double-Blind Study. J Clin Oncol 2010;28(35):5132-9.
Vadhan-Raj S, von Moos R, Fallowfield LJ, et al. Clinical benefit in patients with metastatic bone disease: results of a phase 3 study of denosumab versus zoledronic acid. Ann Oncol 2012;23:3045-51.
July 2018 Updated rationale/uses, dosing considerations in children, adverse effects table, monitoring sections
A Regimen Abstract is an abbreviated version of a Regimen Monograph and contains only top level information on usage, dosing, schedule, cycle length and special notes (if available). It is intended for healthcare providers and is to be used for informational purposes only. It is not intended to constitute or be a substitute for medical advice, and all uses of the Regimen Abstract are subject to clinical judgment. Such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability, and Cancer Care Ontario disclaims all liability for the use of this information, and for any claims, actions, demands or suits that arise from such use.
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