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(DD); AC-PACL(DD)+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 |
PACLITAXEL (Taxol®): (x 4 cycles) | |||
PACLitaxel | 175 mg /m² | IV | Day 1 |
| |||
trastuzumab | 8 mg /kg | IV loading dose | Day 1, cycle 1 only |
THEN, | |||
trastuzumab | 6 mg /kg | IV maintenance dose | Every 21 days |
Alternate trastuzumab schedule (Every 14 days)*: Start concurrently with paclitaxel: | |||
trastuzumab * | 8 mg /kg | IV loading dose | Day 1, with cycle 1 of paclitaxel |
THEN, | |||
trastuzumab * | 4 mg /kg | IV maintenance dose | Every 14 Days, with cycles 2-4 of paclitaxel |
Two weeks after cycle 4 of paclitaxel, continue with single agent trastuzumab 6 mg/kg IV q3 weeks. Refer to TRAS regimen. *Breast Drug Advisory Committee consensus.There may be other clinically appropriate q14 day trastuzumab dosing regimens. Refer to local protocols.
Start concurrently with paclitaxel: | |||
trastuzumab | 4 mg /kg | IV loading dose | Day 1, with cycle 1 of paclitaxel |
THEN, | |||
trastuzumab | 2 mg /kg | IV maintenance dose | Weekly |
One week after cycle 4 of paclitaxel, continue with single agent trastuzumab 6 mg/kg IV q3 weeks. Refer to TRAS regimen. |
REPEAT EVERY 14 DAYS: AC X 4 cycles then Paclitaxel (Taxol®) X 4 cycles
Trastuzumab: For a usual treatment duration of one year unless limited by cardiotoxicity risk. Refer to TRAS regimen for trastuzumab continuation after AC-PACL(DD).
High (AC)
Low (Paclitaxel)
High
Primary prophylaxis with G-CSF is indicated for AC-PACL(DD). Refer to the Febrile neutropenia guideline.
Other Supportive Care:
Also refer to CCO Antiemetic Recommendations.
Pre-medications* (prophylaxis for infusion reaction with paclitaxel):
- Dexamethasone 20 mg PO 12-and 6-hours OR Dexamethasone 20 mg IV 30 minutes pre-infusion†
- Diphenhydramine 25-50 mg IV/PO 30-60 minutes pre-infusion
- Ranitidine 50 mg IV OR Famotidine 20 mg IV 30-60 minutes pre-infusion
* Consider discontinuing pre-medications for paclitaxel if there was no IR in the first 2 doses.
† Oral and IV dexamethasone are both effective at reducing overall IR rates. Some evidence suggests that oral dexamethasone may be more effective for reducing severe reactions; however, adverse effects and compliance remain a concern.
Doses should be modified according to the protocol by which the patient is being treated.
Refer to TRAS (Breast - Adjuvant) regimen for details on trastuzumab dose modifications.
Dosage with toxicity
Hematologic Toxicities: See general recommendations.
Toxicity Type / Counts x 109/L |
| Toxicity Type / Counts x 109/L | Doxorubicin (% previous dose) | Cyclophosphamide (% previous dose) | Paclitaxel (% previous dose) |
ANC <1.5 | Or | Platelet < 100 | Hold * | ||
Febrile Neutropenia, or | Or | Thrombocytopenic bleeding | Hold * then 75% | ||
ANC ≥ 1.5 | And | Platelet ≥ 100 | 100% | ||
Grade 3/4 Neurotoxicity
|
|
| Not applicable | 80%* | |
Grade 3 related organ |
|
| *75% for suspect drug(s). If cardiotoxicity, follow recommendations in doxorubicin and paclitaxel drug monographs. | ||
Grade 4 related organ |
|
| Discontinue |
Hepatic Impairment
Bilirubin |
| AST/ALT | Cyclophosphamide | Doxorubicin | Paclitaxel |
(% of previous / mg/m2) | |||||
1-2 x ULN | and/ or | - | 100% | 50% | 100% |
2-4 x ULN | 2-4 xULN | Caution | 25% | 135mg/m2 | |
>4 x ULN | >4 x ULN | Caution | Discontinue | 50mg/m2 or OMIT |
Renal Impairment
Creatinine Clearance (mL/min) | Cyclophosphamide | Doxorubicin | Paclitaxel |
(% of previous) | |||
>30-50 | 100% | 100% | 100% |
10-30 | 50-75% | 100% | 100% |
<10 | 50% or OMIT | 100% | 100% |
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).
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 DOXOrubicin, cyclophosphamide, filgrastim, 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.
Refer to TRAS (Breast - Adjuvant) regimen for details on trastuzumab clinical monitoring.
Recommended Clinical Monitoring
- Clinical toxicity assessment (including stomatitis, cardiotoxicity, local toxicity, cystitis, hypersensitivity, neuropathy, musculoskeletal, infection or diarrhea); at each visit
- CBC before each cycle
- Baseline and regular liver function tests
- Baseline and regular renal function tests and urinalysis
- Cardiac examination especially with risk factors (including prior therapy with Epirubicin, Mitoxantrone, or other cardiotoxic drug), or a cumulative doxorubicin dose of > 450 mg/m2
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
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Citron M, Berry D, Cirrincione C, et al. Randomized trial of dose dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: First Report of Intergroup Trial C9741/Cancer and Leukemia Group B trial 9741. J Clin Oncol; 2003 Apr 15. 21(8): 1431-1439.
Doxorubicin, cyclophosphamide, paclitaxel drug monographs, Cancer Care Ontario.
February 2022 Removed trastuzumab EBP forms; updated Rationale and uses section, Drug Regimen and Cycle Frequency sections
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.
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