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AC-DOCE; AC-DOCE+TRAS

Cancer Type: Breast  Intent: Neoadjuvant, Adjuvant
Regimen Category: Evidence-Informed
Funding:
New Drug Funding Program
    Docetaxel - FEC-D or AC-DOCE for Adjuvant Treatment for Breast Cancer
New Drug Funding Program
    Docetaxel - Neoadjuvant treatment for Non-Metastatic Breast Cancer
New Drug Funding Program
    Trastuzumab - Adjuvant Treatment for HER2_neu-Overexpressing Primary Breast Cancer
Evidence Building Program
    Trastuzumab (EBP) - Adjuvant Treatment for Breast Cancer
Evidence Building Program
    Trastuzumab (EBP) - Adjuvant Treatment for Breast Cancer Supplemental
A - Regimen Name

AC-DOCE Regimen
ADRIAMYCIN ® (DOXOrubicin)-Cyclophosphamide then DOCEtaxel
AC-DOCE+TRAS Regimen
ADRIAMYCIN ® (DOXOrubicin)-Cyclophosphamide then DOCEtaxel 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

Neoadjuvant treatment for non-metastatic breast cancer (inoperable locally advanced, inflammatory or to downsize tumour pre-surgery) or adjuvant therapy for node-positive and high risk node-negative breast cancer patients. 
Trastuzumab may be used concurrently with docetaxel (after completion of AC) or after completion of docetaxel in:

  • high-risk (node-positive or negative with tumour > 1cm) HER-2 positive breast cancer
  • or small tumours (≤1 cm, node negative) in HER-2 positive breast cancer as part of the evidence building program

Supplementary Public Funding

DOCEtaxel
New Drug Funding Program (Docetaxel - FEC-D or AC-DOCE for Adjuvant Treatment for Breast Cancer)

DOCEtaxel
New Drug Funding Program (Docetaxel - Neoadjuvant treatment for Non-Metastatic Breast Cancer)

trastuzumab
New Drug Funding Program (Trastuzumab - Adjuvant Treatment for HER2_neu-Overexpressing Primary Breast Cancer)

trastuzumab
Evidence Building Program (Trastuzumab (EBP) - Adjuvant Treatment for Breast Cancer)

trastuzumab
Evidence Building Program (Trastuzumab (EBP) - Adjuvant Treatment for Breast Cancer Supplemental)

 
B - Drug Regimen

AC: (x 4 cycles)

DOXOrubicin

(Round to nearest 1mg)
60 mg /m² IV Day 1
cyclophosphamide

(Round to nearest 10mg)
600 mg /m² IV Day 1

THEN

Docetaxel (Taxotere®): (x 4 cycles)

DOCEtaxel

(Round to nearest 5mg)
100 mg /m² IV Day 1


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

trastuzumab
Refer to TRAS (Breast - Adjuvant) regimen for details.
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C - Cycle Frequency

REPEAT EVERY 21 DAYS

AC X 4 cycles then Docetaxel (Taxotere®) X 4 cycles

Trastuzumab: Refer to TRAS (Breast - Adjuvant) regimen for details.

 
D - Premedication and Supportive Measures

Antiemetic Regimen:

High (AC)
Low (Docetaxel)


Febrile Neutropenia Risk:

High

Consider G-CSF prophylaxis for patients at high risk of febrile neutropenia. See G-CSF recommendations.


Other Supportive Care:

  • With docetaxel cycles: Dexamethasone 8 mg bid po for 3 days starting 1 day prior to docetaxel (prevent anaphylaxis / fluid retention.)
  • With docetaxel, consider antibiotic prophylaxis or G-CSF according to local guidelines
  • Trastuzumab: Refer to Trastuzumab drug monograph for full details.
 
E - Dose Modifications

Doses should be modified according to the protocol by which the patient is being treated. The following recommendations have been adapted from clinical trials or product monographs and could be considered.

See TRAS (Breast - Adjuvant) regimen for details on trastuzumab dose modifications.

Dosage with toxicity

Worst Toxicity Type / Counts x 109/L

 

Worst Toxicity Type / Counts x 109/L

Doxorubicin
(% previous dose)

 

Cyclophosphamide
(% previous dose)
Docetaxel
(% previous dose)

ANC < 0.5
≥ 7 days, or
Febrile neutropenia

Or

Thrombocytopenic bleeding

 Hold*, then 75%
(or consider GCSF – for isolated neutropenia)
 Hold*, then 75%
(or consider GCSF – for isolated neutropenia)

Grade 3 Neurotoxicity

or

Grade 3 skin toxicity

Not applicable

75%*;
Discontinue if recurs

 

Cystoid macular edema

 

 

    Not applicable

Hold and investigate; refer patient promptly an ophthalmic examination. Discontinue if confirmed.

 

Worst Toxicity Type / Counts x 109/L   Worst Toxicity Type / Counts x 109/L Doxorubicin
(% previous dose)
Cyclophosphamide
(% previous dose)
Docetaxel
(% previous dose)

Other Grade 3 related organ / non-hematologic

 

 

75%* for suspect drug(s). If cardiotoxicity, follow recommendations in doxorubicin drug monograph.

Grade 4 related organ / non-hematologic

 

 

Discontinue 

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



Hepatic Impairment

 
AST and/or ALT
 
Alk Phosp
Cyclophosphamide (% previous)
Doxorubicin (% previous)
Docetaxel (% previous)
 
Mild-moderate
> 1.5 -3.5 X ULN
AND
> 2.5 to 6 x ULN
100%; caution with moderate hepatic impairment 50-75%
Do not treat

 

Severe
> 3.5 x ULN
OR
> 6 x ULN
Caution Discontinue
Do not treat. Discontinue* if treatment already started.
*Discontinue if Bilirubin > ULN and any AST/ALT, Alk phosp

Renal Impairment

Creatinine Clearance (mL/min)

DOXOrubicin

(% previous dose)

cyclophosphamide

(% previous dose)

DOCEtaxel

(% previous dose)

>50

 No change

 100%

 No change

10-50                         

 No change

 75%

 No change

<10

 No change

Use with extreme caution or discontinue

 No change


Dosage in the Elderly

No dosage adjustment required, but caution should be exercised in elderly patients with poor performance status who are receiving docetaxel.

The risk of cardiac dysfunction and myelosuppression may be increased in elderly patients on trastuzumab. The reported trials did not determine differences in efficacy between patients > 65 years versus younger patients.

 


 
F - Adverse Effects

Refer to DOXOrubicin, cyclophosphamide, DOCEtaxel (± trastuzumab) drug monograph(s) for additional details of adverse effects
 


Most Common Side Effects 

Less Common Side Effects, but may be
Severe or Life-Threatening

  • Nausea and vomiting, diarrhea, stomatitis
  • Cystitis
  • Myelosuppression ± infection, bleeding (may be severe)
  • Alopecia
  • Hypersensitivity (may be severe)
  • Fluid retention (may be severe)
  • Neuropathy (may be severe)
  • Cutaneous (may be severe)
  • Fatigue
  • Musculoskeletal pain
  • ↑ LFTs (may be severe)
  • Lacrimation / lacrimal duct obstruction
  • Cardiotoxicity
  • Secondary malignancies
  • Arterial thromboembolism
  • Venous thromboembolism
  • Pneumonitis
  • GI perforation/obstruction
  • SIADH
  • DIC, hemolytic uremic syndrome
  • Rhabdomyolysis
  • Cystoid macular edema
 
G - Interactions
Refer to DOXOrubicin, cyclophosphamide, DOCEtaxel (± trastuzumab) drug monograph(s) for additional details
 
H - Drug Administration and Special Precautions

Refer to DOXOrubicin, cyclophosphamide, DOCEtaxel (± trastuzumab) drug monograph(s) for additional details


 

 

 
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.

Recommended Clinical Monitoring

  • CBC; baseline and 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
  • Clinical toxicity assessment (including stomatitis, cardiotoxicity, local toxicity, cystitis, neurologic, infection, bleeding, skin and nails, hypersensitivity, GI, respiratory, fatigue, fluid retention, ophthalmic, musculoskeletal pain, thromboembolism); at each visit
  • 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-DOCE
AC: 1 to 1.5 hours; DOCE: 2 hours
AC-DOCE+TRAS
AC: 1 to 1.5 hours; DOCE: 2 hours; TRAS: First cycle - 1.5 hours; Subsequent cycles - 0.5 hour
Pharmacy Workload (average time per visit)
AC-DOCE
27.25 minutes
AC-DOCE+TRAS
32.595 minutes
Nursing Workload (average time per visit)
AC-DOCE
55.417 minutes
AC-DOCE+TRAS
65.417 minutes
 
K - References

Bear HD, Anderson S, Brown A, et al. The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol 2003;21(22):4165-74.

Eiermann W, Pienkowski T, Crown J, et al. Phase III study of doxorubicin/cyclophosphamide with concomitant versus sequential docetaxel as adjuvant treatment in patients with human epidermal growth factor receptor 2-normal, node-positive breast cancer: BCIRG-005 trial. J Clin Oncol 2011;29(29):3877-84.

Slamon D, Eiermann W, Robert N, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med 2011;365(14):1273-83.

Swain SM, Jeong JH, Geyer CE Jr, et al. Longer therapy, iatrogenic amenorrhea, and survival in early breast cancer. N Engl J Med 2010;362(22):2053-65.


PEBC Advice Documents or Guidelines

February 2018 edited NDFP forms


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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.
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