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TEMS
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.
Treatment of metastatic renal cell carcinoma. It is recommended and funded for first-line, poor-risk (defined by Mekhail criteria) metastatic renal cell cancer.
temsirolimus
New Drug Funding Program
(Temsirolimus - Metastatic Renal Cell Carcinoma)
Minimal
Other Supportive Care:
- Diphenhydramine 25 to 50mg IV should be given 30 minutes before the start of the temsirolimus infusion.
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.
Do not administer if bilirubin > 1.5 x ULN.
Dosage with toxicity
|
Toxicity and Grade |
Action |
Dose |
|
Pneumonitis (grade 1 or 2) |
Hold until ≤ grade 1; may continue if asymptomatic. Consider steroids. |
Consider dose reduction (5mg/week) |
|
Pneumonitis (grade 3 or 4) |
Discontinue, consider steroids |
Discontinue permanently |
|
Intolerable grade 2 non-hematological |
May continue AND |
Reduce by 5mg/week* |
|
Grade 3 or 4 non-hematological |
Hold until recovered to ≤ grade 2 AND |
Reduce by 5mg/week* |
|
Platelet < 75 x 109/L and/or ANC < 1 x 109/L |
Hold until recovery to ≥ 75 x 109/L and ≥1 x 109/L AND |
Reduce by 5mg/week* |
| Grade | Action |
| Grade 1 or 2 |
|
| Grade 3 or 4 |
|
Hepatic Impairment
Hepatic metabolism / excretion is significant.
|
|
AST |
Bilirubin |
Action |
|
Mild |
> ULN |
≤ ULN |
Caution. Dose at 15mg |
|
|
|
>1 - 1.5 x ULN |
Caution. Dose at 15mg |
|
Moderate to severe |
|
>1.5 x ULN |
Do not treat. |
Renal Impairment
Use with caution. No formal studies have been performed in renally impaired patients. Dose adjustment may not be required since <5% of the dose is excreted in the urine. Temsirolimus use in hemodialysis was described in a case series.
Refer to temsirolimus drug monograph(s) for additional details of adverse effects
|
Very common (≥ 50%) |
Common (25-49%) |
Less common (10-24%) |
Uncommon (< 10%), but may be severe or life-threatening |
|
|
|
|
Refer to temsirolimus drug monograph(s) for additional details
- Avoid concomitant usage with CYP3A4/5 inducers or strong CYP3A4 inhibitors. If the strong CYP3A4 inhibitor cannot be discontinued, consider temsirolimus dose reduction (to 12.5mg /week).
- Caution and monitor for toxicity with CYP3A4/5, CYP2D6 and Pgp substrates
- Extreme caution with anticoagulants due to increased risk of CNS bleeding in patients with CNS tumours
- Caution with ACE inhibitors or calcium channel blockers due to increased risk of angioneurotic edema
- Avoid QT prolonging drugs if possible
Refer to temsirolimus drug monograph(s) for additional details
Administration:
- Inject supplied diluent (contains polysorbate 80 and PEG 400) into the drug vial and then dilute further in 250mL Normal Saline, infuse over 30 -60 minutes. Avoid excessive shaking as this may cause foaming.
- To decrease di-(2-ethylhexyl) phthalate (DEHP) leaching or avoid excessive drug loss, materials used in administration must be composed of glass, polyolefin or polyethylene. Use a non-PVC non-DEHP tubing, including an in-line polyethersulfone filter ≤ 5 microns. A polyethersulfone end-filter (0.2 to 5 microns) may be added if the administration set does not have an in-line filter component. The use of both an in-line and end-filter is not recommended.
- The drug concentrate-diluent mixture is stable for up to 24 hours at room temperature and protected from light. The final diluted drug solution should be completely administered within 6 hours from the time that the concentrate-diluent mixture is added to the Normal Saline bag.
- Keep unopened drug and diluent vials refrigerated (2-8°C); do not freeze.
- Protect the drug and diluted solutions from light. Do not use if drug is discoloured or if particulates are present.
Contraindications:
- patients with known hypersensitivity to this sirolimus, temsirolimus, or any ingredients in the formulation
- patients with elevated bilirubin (> 1.5 x ULN)
Other Warnings/Precautions:
- patients with pre-existing or at risk of prolonged QTc
- patients with brain metastases (increased risk of bleeding)
- patients who have known hypersensitivity to an antihistamine or cannot receive an antihistamine for other medical reasons
- patients on anticoagulants or who have had recent surgery
- avoid use of live vaccines
- Temsirolimus should not be used in pregnancy. Adequate contraception should be used by both sexes during treatment, and for at least 3 months after the last dose.
- Breastfeeding is not recommended
Recommended Clinical Monitoring
- CBC; baseline and weekly
- Lipids and fasting glucose; baseline and routine
- Liver function tests; baseline and regular (every 2 weeks)
- Renal function tests & electrolytes; baseline and regular (every 2 weeks)
- Routine assessment for signs and symptoms of fatigue, hyperglycemia, bleeding, pneumonitis, fluid retention, skin toxicity, infections, mucositis, delayed wound healing, infusion reactions, rhabdomyolysis (especially with statins); regular
-
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
Suggested Clinical Monitoring
- Radiology (screening for ILD); baseline and periodic
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Hudes G, Carducci M, Tomczak P, et al. Temsirolimus, Interferon Alfa, or Both for Advanced Renal-Cell Carcinoma. N Engl J Med 2007;356:2271-81.
Mekhail TM, Abou-Jawde RM, BouMerhi G, et al. Validation and extension of the Memorial Sloan-Kettering prognostic factors model for survival in patients with previously untreated metastatic renal cell carcinoma. J Clin Oncol. 2005;23:832-41.
Temsirolimus drug monograph, Ontairo Health (Cancer Care Ontario).
July 2020 Modified Drug administration section
Regimen Abstracts
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.
Information in regimen abstracts is accurate to the extent of the ST-QBP regimen master listings, and has not undergone the full review process of a regimen monograph. Full regimen monographs will be published for each ST-QBP regimen as they are developed.
Regimen Monographs
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
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