Drug Formulary information is intended for use by healthcare professionals. It is not intended to be medical advice. Some of the information, including information about funding for cancer drugs, does not apply to all patients. Cancer treatment plans are unique to each patient. If you are a patient, please speak with your healthcare team to understand how this information applies to you.
AC-PACL(W); AC-PACL(W)+TRAS
Adjuvant
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.
Neo-adjuvant or adjuvant treatment for node-positive and high risk node-negative early breast cancer.
Trastuzumab may be used concurrently with paclitaxel or after completion of paclitaxel in HER-2 positive breast cancer.
trastuzumab
New Drug Funding Program
(Trastuzumab (Biosimilar) - Adjuvant Treatment for Breast Cancer)
Note: Different trastuzumab products are not interchangeable.
AC: (x 4 cycles)
DOXOrubicin | 60 mg /m² | IV | Day 1 |
cyclophosphamide | 600 mg /m² | IV | Day 1 |
Repeat Every 21 Days THEN PACLITAXEL Weekly: (x 12 doses) |
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PACLitaxel | 80 mg /m² | IV | Day 1 |
Repeat Every 7 Days For patients with HER2 positive tumours, Trastuzumab may be given for one year, starting concurrently with paclitaxel or after 12 weekly cycles of paclitaxel: |
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trastuzumab | 8 mg /kg | IV loading dose | Day 1, cycle 1 only |
THEN, |
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trastuzumab | 6 mg /kg | IV maintenance dose | Every 21 Days |
Alternative chemotherapy schedule: AC: (x 4 cycles) |
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DOXOrubicin | 60 mg /m² | IV | Day 1 |
cyclophosphamide | 600 mg /m² | IV | Day 1 |
Repeat Every 14 Days THEN PACLITAXEL Weekly: (x 12 doses) |
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PACLitaxel | 80 mg /m² | IV | Day 1 |
Repeat Every 7 Days
Alternative Trastuzumab schedule: For patients with HER2 positive tumours, Trastuzumab may be given for one year, starting concurrently with paclitaxel or after 12 weekly cycles of paclitaxel: |
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trastuzumab | 4 mg /kg | IV loading dose | Day 1, cycle 1 only |
THEN, |
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trastuzumab | 2 mg /kg | IV maintenance dose | Weekly (Q7 Days) |
AC X 4 cycles then weekly Paclitaxel (Taxol®) X 12 doses
Q3 Weeks or Weekly Trastuzumab: Refer to TRAS (Breast - Adjuvant) regimen for details.
High (AC)
Low (Paclitaxel)
Low
AC(Q3W)-PACL(W)
High
AC(Q2W)-PACL(W): Use G-CSF prophylaxis for patients at high risk of febrile neutropenia. See G-CSF recommendations.
Other Supportive Care:
• Paclitaxel: Patients should be pretreated with a corticosteroid as well as an antihistamine and a H2 Blocker. For example:
- Dexamethasone 10mg IV 30 minutes before Paclitaxel
- Diphenhydramine 50mg IV 30 minutes before Paclitaxel
- Ranitidine 50mg IV 30 minutes before Paclitaxel
Also refer to CCO Antiemetic Summary
Doses should be modified according to the protocol by which the patient is being treated. The following recommendations are in use at some centres.
Dosage with toxicity
Hematologic Toxicities: See Appendix 6 for general recommendations.
Suggested Dose Levels:
Doxorubicin: 60 mg/m², 45 mg/m², 30 mg/m²
Cyclophosphamide: 600 mg/m², 450 mg/m², 300 mg/m²
Paclitaxel: 80 mg/m², 60 mg/m², 40 mg/m²
Toxicity Type / Counts x 109/L |
|
Toxicity Type / Counts x 109/L |
Doxorubicin*
|
Cyclophosphamide* |
Paclitaxel*
|
ANC < 1.5 |
Or |
Platelet < 100 |
Hold* |
Hold* |
Hold* |
Febrile Neutropenia |
Or |
ANC < 0.5 |
Hold* and ↓ 1 dose level or GCSF |
Hold* and ↓ 1 dose level or GCSF |
Hold* and ↓ 1 dose level or GCSF |
Grade 3 neurotoxicity |
|
|
100% |
100% |
↓ 1 dose level * |
Other Grade 3 non-hematologic |
|
|
↓ 1 dose level* |
↓ 1 dose level* |
↓ 1 dose level* |
Grade 4 non-hematologic |
|
|
Discontinue |
Discontinue |
Discontinue |
* Major organ toxicity should have recovered to ≤ grade 2, ANC to ≥ 1.5 x 109/L and platelets ≥ 100 x 109/L prior to retreatment.
|
Hepatic Impairment
Bilirubin * |
Doxorubicin |
Cyclophosphamide |
Paclitaxel |
1-2 X ULN |
50% |
No adjustment required |
Caution |
2-4 X ULN |
25% |
Caution |
75% |
> 4 X ULN |
OMIT |
Caution |
50% or OMIT |
*Consider dose reduction for doxorubicin and paclitaxel for severe increase(s) in transaminases.
Renal Impairment
Creatinine Clearance (mL/min) |
Doxorubicin |
Cyclophosphamide (% previous dose) |
Paclitaxel |
>30 – 50 |
No adjustment required |
100% |
No adjustment required |
10 – 30 |
50 – 75% |
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<10 |
50% or OMIT |
Refer to DOXOrubicin, cyclophosphamide, PACLitaxel drug monograph(s) for additional details of adverse effects
Refer to trastuzumab drug monograph for adverse effect details (not listed below).
Most Common Side Effects |
Less Common Side Effects, but may be |
|
|
Refer to DOXOrubicin, cyclophosphamide, PACLitaxel drug monograph(s) for additional details
Refer to DOXOrubicin, cyclophosphamide, PACLitaxel drug monograph(s) for additional details
Note: Different trastuzumab products are not interchangeable.
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
- CBC; baseline and before each cycle
- Liver function tests; baseline and before each cycle
- Renal function tests and urinalysis; baseline and before each cycle
- Cardiac function tests (echocardiogram or MUGA scan) and examination especially with risk factors (including prior therapy with epirubicin, mitoxantrone, or other cardiotoxic drug), or a cumulative doxorubicin dose of > 450 mg/m2; baseline and regular
- Blood pressure and pulse rate monitoring during paclitaxel infusion; baseline and as clinically indicated
- Clinical toxicity assessment, including GI toxicity, cardiotoxicity, local toxicity, cystitis, hypersensitivity, neurotoxicity, musculoskeletal effects; at each visit
-
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
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Doxorubicin, cyclophosphamide, paclitaxel and trastuzumab drug monographs, Cancer Care Ontario.
Henderson IC, Berry D, Demetri G, Cirrincione C, et al. Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol 2003; 21(6): 976-83.
Romond EH, Perex EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. NEJM 2005; 353(16) 1673-84.
Sparano JA, Wang M, Martino S, et al. Weekly paclitaxel in the adjuvant treatment of breast cancer. NEJM 2008; 358(16): 1663-71.
February 2022 Removed trastuzumab EBP forms; updated Rationale and uses 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.