Les renseignements du Formulaire de médicaments s’adressent aux professionnels de la santé. Il ne s’agit pas d’un avis médical. Certains des renseignements, y compris ceux sur le financement des médicaments anticancéreux, ne s’appliquent pas à tous les patients. Les plans de traitement du cancer sont propres à chaque patient. Si vous êtes un patient, veuillez parler avec votre équipe soignante pour comprendre comment ces renseignements s’appliquent à vous.
PGLDX
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.
Monotherapy for patients with metastatic breast cancer, where there is an increased cardiac risk associated with conventional doxorubicin
| pegylated liposomal DOXOrubicin | 40-50 mg /m² | IV | Day 1 |
| (This drug is not publicly funded. Universal compassionate access program is available. ) | |||
REPEAT EVERY 28 DAYS
Until disease progression or unacceptable toxicity, or limited by cardiotoxicity
Doses should be modified according to the protocol by which the patient is being treated.
Dosage with toxicity
Dose adjustment is required in patients with history of prior anthracyclines use, prior mediastinal irradiation, concurrent cyclophosphamide therapy, or pre-existing cardiovascular disease.
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Worst Toxicity & Toxicity on day of planned dosing |
Action*: Week 4-5
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Action*: Week 6
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Grade 1 skin/stomatitis
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If was ≥ grade 3, delay for 1-2 weeks; otherwise treat on time
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If still grade 1, ↓ dose by 25%
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Grade 2 skin/stomatitis
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Delay for 1-2 weeks;
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If still grade 1 or 2, ↓ dose by 25%
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Grade 3 or 4 skin/stomatitis
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Delay for 1-2 weeks;
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Discontinue if still ≥ grade 3
Consider discontinuing if was grade 4
Otherwise ↓ dose by 25%
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Grade 4 ANC, platelets, febrile neutropenia or thrombocytopenic bleeding |
↓ dose by 25%
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Significant cardiotoxicity
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Discontinue
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Grade 3 other
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↓ dose by 25%
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Grade 4 other
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Discontinue
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*Do not retreat until ANC > 1.5 x 109/L, platelets > 75-100 x 109/L and other toxicity ≤ grade 2 / or as indicated above |
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Management of Infusion-related reactions with Anthracyclines:
| Grade | Management | Re-challenge |
| 1 or 2 |
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| 3 or 4 |
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Hepatic Impairment
|
Bilirubin
(µmol/L)
|
Cycle 1 (% standard dose) |
Cycle 2 onwards (if cycle 1 tolerated with no changes in liver function) (% standard dose) |
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21-51
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75%
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100%
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>51
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50%
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75%*
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* The dosage can be increased for subsequent cycles if tolerated.
Renal Impairment
No modifications are necessary for mild to moderate renal impairment (creatinine clearance > 30 mL/min). No studies have been done in patients with severe renal impairment.
Dosage in the Elderly
Limited information in patients ≥ 60 years. Use with caution.
Refer to pegylated liposomal DOXOrubicin drug monograph(s) for additional details of adverse effects
| Most Common Side Effects |
Less Common Side Effects, but may be |
|
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Refer to pegylated liposomal DOXOrubicin drug monograph(s) for additional details
Administration:
Pegylated liposomal doxorubicin must not be given by the intramuscular or subcutaneous route.
- For dose < 90mg, dilute drug in 250mL D5W.
- For dose ≥ 90mg, dilute drug in 500mL D5W.
- Only use 5% Dextrose solution for further dilution. Use of other diluents or ones containing bacteriostatic agents (i.e. benzyl alcohol) may cause drug precipitation.
- Do not administer as a bolus injection or undiluted solution. The Caelyx® infusion line can be connected through the side port of a 5% Dextrose infusion for further diluent, or to minimize risk of thrombosis or extravasation.
- Do not use in-line filters. Do not admix with other drugs.
- To minimize the risk of infusion reactions, the initial dose is administered at a rate no greater than 1 mg/minute. If no infusion reaction is observed, subsequent infusions may be administered over 60-minutes.
- The following graduated rate was used for patients who experienced an infusion reaction in the breast clinical trial: 5% of the total dose infused IV over 15 minutes. If tolerated, double the infusion rate for the next 15 minutes. If tolerated, complete the infusion over the next hour for a total infusion time of 90 minutes.
- Avoid extravasation. It may occur with or without an accompanying stinging or burning sensation, and even if blood returns well on aspiration of the infusion needle. If any signs or symptoms of extravasation occur, the injection or infusion should be immediately terminated and restarted in another vein. Any known or suspected extravasation should be managed promptly.
Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.
Contraindications:
- patients who have a history of hypersensitivity reactions to a conventional formulation of doxorubicin, other anthracyclines, anthracenediones, or components of the pegylated liposome
Other Warnings/ Precautions:
- use with caution in patients with a history of cardiovascular disease and/or prior anthracycline use
- care should be exercised in patients with diabetes as the infusate is dextrose water
- pegylated liposomal doxorubicin (Caelyx) is a unique formulation of doxorubicin and should never be used interchangeably with other formulations of doxorubicin
Pregnancy and Lactation:
- Pegylated liposomal doxorubicin is not recommended for use in pregnancy. Adequate contraception should be used by both sexes during treatment, and for at least 6 months after the last dose.
- Pegylated liposomal doxorubicin is contraindicated in breastfeeding.
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
- Cardiac function tests (Echo, RNA and/or MUGA scans) for all patients with cardiac risk factors; baseline and as clinically indicated. Regular cardiac function tests before each additional dose over the cumulative dose threshold of 450 mg/m2. (Cumulative dose lower for high risk patients.)
- CBC; baseline and at each visit
- Liver function tests; baseline and at each visit
- Clinical assessment of stomatitis, rash, hand-foot syndrome, hypersensitivity, infection, bleeding, cardiac symptoms; at each visit
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Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
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O'Brien ME, Wigler N, Inbar M et al. Reduced cardiotoxicity and comparable efficacy in a phase III trial of pegylated liposomal doxorubicin HCl (CAELYX®/Doxil®) versus conventional doxorubicin for first-line treatment of metastatic breast cancer. Ann Oncol. 2004 Mar;15(3):440-9.
Pegylated doxorubicin drug monograph, Cancer Care Ontario.
December 2019 Updated infusion reaction information in Dose Modification 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.
While care has been taken in the preparation of the information contained in the Formulary, 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.
CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.