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.
PACL(W); PACL(W)+TRAS
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 the treatment of metastatic breast cancer
trastuzumab
New Drug Funding Program
(Trastuzumab (Biosimilar) in combination with Chemotherapy - Metastatic Breast Cancer)
(NDFP Website
)
trastuzumab
New Drug Funding Program
(Trastuzumab (Biosimilar) - Second Line - Metastatic Breast Cancer)
| PACLitaxel | 80 mg /m² | IV | Days 1, 8, 15 |
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For patients with HER2 positive tumours, trastuzumab may be given concurrently with paclitaxel and then as a single agent |
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| trastuzumab | 8 mg /kg | IV loading dose | Day 1, cycle 1 only |
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THEN, |
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| trastuzumab | 6 mg /kg | IV maintenance dose | Every 21 days |
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| trastuzumab | 4 mg /kg | IV loading dose | Day 1, cycle 1 only |
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THEN, |
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| trastuzumab | 2 mg /kg | IV maintenance dose | Weekly (Q7 Days) |
Paclitaxel: REPEAT EVERY 28 DAYS until disease progression or unacceptable toxicity.
Q3 Weekly or Weekly Trastuzumab: See TRAS (Breast - Advanced) regimen for details.
Low
Other Supportive Care:
Also refer to CCO Antiemetic Recommendations.
Paclitaxel Pre-medications* (prophylaxis for infusion reaction):
To be given 30-60 minutes prior to paclitaxel infusion.
- Dexamethasone 10 mg IV, starting in cycle 1
- Diphenhydramine 25-50 mg IV/PO
- Ranitidine 50 mg IV OR Famotidine 20 mg IV
* Consider discontinuing pre-medications for paclitaxel if there was no IR in the first 2 doses.
Doses should be modified according to the protocol by which the patient is being treated.
See TRAS (Breast - Advanced) regimen for details on trastuzumab dose modifications.
Dosage with toxicity
Dose levels: 80 mg/m², 70 mg/m², 60 mg/m². Dose re-escalations are not allowed. Discontinue treatment if toxicity recurs after 2 dose reductions.
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Toxicity (Grade or Counts x 109/L)
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Paclitaxel dose | |
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ANC < 1.5 and/or Platelets < 100
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Delay1
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ANC ≤ 0.8 and/or Platelets ≤ 50
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Delay1; ↓ 1 level for next dose
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Grade 2 neurotoxicity
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↓ 1 level
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Other Grade 2-3 non-hematological2, 3 or grade 3 neurotoxicity
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Delay1; ↓ 1 level
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Grade 4 non-hematological3; more than 2 weeks delay or more than 2 dose reductions
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Discontinue
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2 Except alopecia, fatigue and nausea. Appropriate symptom management should be provided for vomiting, diarrhea, constipation; dose modifications may not be necessary.
Management of Infusion-related reactions:
Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.
Paclitaxel:
| Grade | Management | Re-challenge |
| 1 or 2 |
Restart:
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| 3 or 4 |
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Hepatic Impairment
For paclitaxel, patients with hepatic impairment may be at risk of toxicity, especially myelosuppression (see table for suggested dosage adjustment). No dosage adjustment required for trastuzumab.
| Bilirubin and/or AST/ALT | Dose (mg/m2) |
| 2-4 x ULN | 60 |
| >4 x ULN | 40 or omit |
Renal Impairment
No adjustment required for paclitaxel, but may consider for patients with HIV-AIDS if creatinine ≥ 2 x ULN. No dosage adjustment required for trastuzumab.
Dosage in the Elderly
No adjustment required. Elderly patients are more at risk for severe toxicity with paclitaxel and increased risk for cardiac dysfunction and myelosuppression with trastuzumab.
Refer to PACLitaxel (± trastuzumab) drug monograph(s) for additional details of adverse effects.
See TRAS (Breast - Advanced) regimen for details on trastuzumab adverse effects.
Paclitaxel:
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Very common (≥ 50%) |
Common (25-49%) |
Less common (10-24%) |
Uncommon (< 10%), but may be severe or life-threatening |
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Refer to PACLitaxel (± trastuzumab) drug monograph(s) for additional details.
See TRAS (Breast - Advanced) regimen for details on trastuzumab drug interactions.
- Caution with concurrent use of paclitaxel with CYP2C8/3A4 substrates, inhibitors and inducers.
Refer to PACLitaxel (± trastuzumab) drug monograph(s) for additional details.
See TRAS (Breast - Advanced) regimen for details on trastuzumab Drug Administration and Special Precautions.
Paclitaxel:
Administration
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In order to minimize patients’ exposure to DEHP leaching from PVC bags or sets, use polyolefin or polypropylene infusion bags and polyethylene-lined administration sets (with a 0.22 micron in-line filter).
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Dilute in Normal Saline or 5% Dextrose, in a final concentration of 0.3-1.2 mg/mL and infuse over 3 hours.
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For weekly dosing, may be infused over 1 hour - mix in 250mL bag as above (not approved by manufacturer).
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Extended infusion of paclitaxel is not recommended as primary prophylaxis to reduce paclitaxel IRs.
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Excessive shaking, agitation, or vibration may induce precipitation and should be avoided.
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Precipitation may rarely occur with infusions longer than 3 hours.
Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.
Contraindications:
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Patients with a history of severe hypersensitivity reactions to paclitaxel or other drugs formulated in Cremophor EL (polyethoxylated castor oil)
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Patients with severe baseline neutropenia (<1.5 x 109/L; < 1 x 109/L for patients with AIDS-related Kaposi’s)
Other Warning/Precautions:
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Paclitaxel contains ethanol, and is administered with agents such as antihistamines which cause drowsiness. Patients should be cautioned regarding driving and the use of machinery.
Pregnancy/Lactation:
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Paclitaxel is not recommended for use in pregnancy.
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Adequate contraception should be used by both sexes during treatment, and for at least 6 months after the last dose.
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Breastfeeding is not recommended.
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Fertility effects: Yes
Also refer to TRAS (Breast - Advanced) regimen for details
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
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CBC; Baseline and at each visit
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Liver and renal function tests; Baseline and at each visit
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Blood pressure and pulse rate monitoring during infusion. Cardiac monitoring with prior arrhythmia; Baseline and as clinically indicated
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Clinical toxicity assessment of bleeding, infection, musculoskeletal effects, neurologic (sensory) effects, hypersensitivity and flu-like symptoms; At each visit
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Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
Suggested Clinical Monitoring
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CBC; As clinically indicated
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Liver function tests; As clinically indicated
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Renal function tests (AIDS-related Kaposi's sarcoma); Baseline and before each dose
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Paclitaxel drug monograph, Cancer Care Ontario.
Seidman AD, Berry D, Cirrincione C, et al. Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, With trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of cancer and leukemia group B protocol 9840. J Clin Oncol 2008; 26:1642-9.
Seidman A D, Fornier MN, Esteva FJ, et al. Weekly trastuzumab and paclitaxel therapy for metastatic breast cancer with analysis of efficacy by HER2 immunophenotype and gene amplification. J Clin Oncol 2001; 19(10): 2587-95.
May 2024 Updated NDFP form
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.