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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.

A - Regimen Name

 

AC-PACL(DD) Regimen
ADRIAMYCIN ® (DOXOrubicin)-Cyclophosphamide then PACLitaxel (Dose Dense)
AC-PACL(DD)+TRAS Regimen
ADRIAMYCIN ® (DOXOrubicin)-Cyclophosphamide then PACLitaxel (Dose Dense) and Trastuzumab

 

 

Disease Site
Breast
 

 

 

Intent
Neoadjuvant
Adjuvant

 

 

Regimen Category
Evidence-Informed :

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.

 

 

Rationale and Uses

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.

 

 

 

Supplementary Public Funding

trastuzumab
New Drug Funding Program (Trastuzumab (Biosimilar) - Adjuvant Treatment for Breast Cancer)
 

 

 
B - Drug Regimen

 

Note: Different trastuzumab products are not interchangeable.

AC: (x 4 cycles)

 

DOXOrubicin
 
60 mg /m²IVDay 1
cyclophosphamide
 
600 mg /m²IVDay 1


THEN

PACLITAXEL (Taxol®): (x 4 cycles)

PACLitaxel
 
175 mg /m²IVDay 1


For patients with HER2 positive tumours, Trastuzumab may be given for one year, starting either concurrently with paclitaxel or after 4 cycles of paclitaxel:

trastuzumab
 
8 mg /kgIV loading doseDay 1, cycle 1 only

THEN,

trastuzumab
 
6 mg /kgIV maintenance doseEvery 21 days
 

Alternate trastuzumab schedule (Every 14 days)*:

Start concurrently with paclitaxel:

trastuzumab

*

8 mg /kgIV loading doseDay 1, with cycle 1 of paclitaxel

THEN,

trastuzumab

*

4 mg /kgIV maintenance doseEvery 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.


Alternate trastuzumab schedule (Weekly):

Start concurrently with paclitaxel:

trastuzumab
 
4 mg /kgIV loading doseDay 1, with cycle 1 of paclitaxel

THEN,

trastuzumab
 
2 mg /kgIV maintenance doseWeekly

 

One week after cycle 4 of paclitaxel, continue with single agent trastuzumab 6 mg/kg IV q3 weeks. Refer to TRAS regimen.

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C - Cycle Frequency

 

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).

 

 
D - Premedication and Supportive Measures
 
Antiemetic Regimen:

High (AC)
Low (Paclitaxel)

 
Febrile Neutropenia Risk:

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.

 
E - Dose Modifications

 

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
Grade 4 ANC ≥ 7 d 

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 

*Retreat when toxicities have recovered to ≤ grade 2, platelets ≥ 100 x 109/L, and ANC ≥ 1.5 x 109/L.

 

 

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%

 
F - Adverse Effects

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

  • Alopecia
  • Myelosuppression ± infection, bleeding (may be severe)
  • Nausea and vomiting (more likely with AC)
  • Musculoskeletal pain (more likely with PACL)
  • Hypersensitivity reactions (with PACL)
  • Diarrhea
  • Neuropathy (may be severe; with PACL)
  • Edema
  • ↑ LFTs (with PACL)
  • Fatigue
  • Abdominal pain
  • Anorexia
  • Nail changes
  • ECG changes
  • Dysguesia
  • Dizziness
  • Cystitis (with AC)
  • Mucositis
  • Cardiotoxicity
  • Secondary leukemia/malignancies
  • Arterial/Venous Thromboembolism
  • Pneumonitis
  • SIADH
  • DIC, Hemolytic Uremic Syndrome
  • Rhabdomyolysis
  • Pancreatitis, GI obstruction, perforation
  • Radiation Recall
  • Injection Site reactions
  • Encephalopathy
  • Seizures
  • Vasculitis
  • QTc Prolongation
  • Optic neuritis
  • Cystoid macular edema
 
G - Interactions
Refer to DOXOrubicin, cyclophosphamide, filgrastim, PACLitaxel drug monograph(s) for additional details
 
H - Drug Administration and Special Precautions

Refer to DOXOrubicin, cyclophosphamide, filgrastim, PACLitaxel drug monograph(s) for additional details

 

Note: Different trastuzumab products are not interchangeable.

 
I - Recommended Clinical Monitoring

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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J - Administrative Information
 
Approximate Patient Visit
AC-PACL(DD)
AC: 1 to 1.5 hours; Paclitaxel: 5 hours
AC-PACL(DD)+TRAS
AC: 1 to 1.5 hours; Paclitaxel hours: 5; TRAS: First cycle - 1.5 hours; Subsequent cycles - 0.5 hour
Pharmacy Workload (average time per visit)
AC-PACL(DD)
24.613 minutes
AC-PACL(DD)+TRAS
29.158 minutes
Nursing Workload (average time per visit)
AC-PACL(DD)
55.75 minutes
AC-PACL(DD)+TRAS
65.75 minutes
 
K - References

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

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M - Disclaimer

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.