You are using an outdated browser. We suggest you update your browser for a better experience. Click here for update.
Close this notification.
Skip to main content Skip to search

CYCLDOCE; CYCLDOCE+TRAS

Cancer Type: Breast  Intent: Adjuvant
Regimen Category: Evidence-Informed
Funding:
New Drug Funding Program
    Docetaxel - CYCLDOCE for Early Operable Breast Cancer
New Drug Funding Program
    Trastuzumab (Biosimilar) - Adjuvant Treatment for 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

CYCLDOCE Regimen
DOCEtaxel-Cyclophosphamide
CYCLDOCE+TRAS Regimen
DOCEtaxel-Cyclophosphamide-Trastuzumab


Disease Site
Breast

Intent
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
  • High-risk (node-positive, or node-negative with tumour size ≥ 1cm) early operable breast cancer when anthracyclines are contraindicated (e.g. underlying cardiac history). 
  • Consider for patients with moderate or intermediate risk disease when omission of an anthracycline may be reasonable to spare these patients the risk of cardiotoxicity (Disease site group recommendation).

Trastuzumab may be used concurrently with or after completion of CYCLDOCE if applicable; refer to the TRAS (Breast -Adjuvant) regimen. Phase III evidence for the addition of trastuzumab to CYCLDOCE does not exist, but it is a reasonable option to mitigate cardiotoxicity in certain patients.

 


Supplementary Public Funding

DOCEtaxel
New Drug Funding Program (Docetaxel - CYCLDOCE for Early Operable Breast Cancer) (NDFP Website)

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

Note: Different trastuzumab products are not interchangeable.

DOCEtaxel
75 mg /m² IV Day 1
cyclophosphamide
600 mg /m² IV Day 1

 

For patients with HER2 positive tumours, trastuzumab is given for one year starting either concurrently with or after completion of chemotherapy.

 

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

REPEAT EVERY 21 DAYS

For total of 4 cycles unless unacceptable toxicity occurs

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

 
D - Premedication and Supportive Measures

Antiemetic Regimen:

Moderate


Febrile Neutropenia Risk:

High

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


Other Supportive Care:

Dexamethasone 8 mg bid po for 3 days starting 1 day prior to docetaxel (prevent anaphylaxis / fluid retention.)
  • 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 appendix 6 for general recommendations.

Suggested dose levels for docetaxel are 75 mg/m2, 55 mg/m2, 40 mg/m2
Suggested dose levels for cyclophosphamide are 600 mg/m2, 450 mg/m2, 300 mg/m2
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

Cyclophosphamide*

 

Docetaxel *

 

Febrile Neutropenia or Grade 4 ANC ≥ 7 d

Or

Thrombocytopenic bleeding

Hold* and ↓  1 dose level (or consider GCSF – for isolated neutropenia)

Hold * and ↓ 1 dose level
(or consider GCSF – for isolated neutropenia)

Grade 3 rash

Or

Grade 3 neurotoxicity

100%

↓  1 dose level.*  Discontinue if recurs

Any occurrence of cystoid macular edema     No change Hold and investigate; refer patient promptly to an ophthalmic examination. Discontinue if confirmed.

Other Grade 3 organ / non-hematologic

 

 

↓ 1 dose level*

↓  1 dose level*

Cystitis

 

 

Consider dose reduction

No change

Grade 4 organ / non-hematologic

 

 

Discontinue

Discontinue

* Major organ toxicity should have recovered to ≤ grade 2 , ANC ≥ 1.5 x 109/L and platelets ≥ 100 x 109/L prior to retreatment



Hepatic Impairment

  AST and/or ALT   ALP   Bilirubin Cyclophosphamide (% usual dose) Docetaxel (% usual dose)
Mild-moderate > 1.5 x ULN AND > 2.5x ULN     No change Do not treat
Severe > 3.5 x ULN OR > 6x ULN  OR > ULN Caution Do not treat. Discontinue if treatment already started.
 

Renal Impairment

Creatinine Clearance (mL/min)

Cyclophosphamide (% of previous)

Docetaxel
(% of previous)

>50

100%

100%

10-50

↓ 1 level

100%

<10

↓ 2 levels or OMIT

100%


Dosage in the Elderly

For docetaxel, no adjustment required, but caution should be exercised in elderly patients with poor performance status.

 

For cyclophosphamide, no dose modification routinely required, but should be used with caution.

 


 
F - Adverse Effects

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

The following adverse effects table is related to CYCLDOCE.  Refer to trastuzumab drug monograph for additional details on trastuzumab.


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, vomiting
  • Fatigue
  • Neuropathy (may be severe)
  • Fluid retention
  • Mucositis
  • Diarrhea
  • Nail disorder (may be severe)
  • Rash (may be severe)
  • Hypersensitivity reaction (may be severe)
  • Musculoskeletal pain
  • Arterial / venous thromboembolism
  • Arrhythmia, QT prolongation
  • Cardiotoxicity
  • Eye disorders (including cystoid macular edema, conjunctivitis & tear duct obstruction)
  • Radiation / injection recall and injection site reaction
  • Hand foot syndrome
  • Delayed wound healing
  • Disseminated intravascular coagulation
  • RPLS
  • Seizure
  • Bladder fibrosis
  • Hemorrhagic cystitis
  • GI obstruction / perforation
  • ↑ LFTs
  • Secondary malignancy
  • Pancreatitis
  • Rhabdomyolysis
  • Nephrotoxicity
  • SIADH
  • Adult respiratory distress syndrome (ARDS), pneumonitis
  • Veno-occlusive disease

 

 
G - Interactions

Refer to DOCEtaxel, cyclophosphamidetrastuzumab) drug monograph(s) for additional details

 

 
H - Drug Administration and Special Precautions

Refer to DOCEtaxel, cyclophosphamidetrastuzumab) drug monograph(s) for additional details


Note: Different trastuzumab products are not interchangeable.

 
I - Recommended Clinical Monitoring

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

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 before each cycle
  • Baseline and regular liver function tests
  • Baseline and regular renal function tests and urinalysis
  • Clinical toxicity assessment (including neurologic, musculoskeletal, hypersensitivity, GI, skin and nails, cystitis, fluid retention, infection, bleeding, fatigue, thromboembolism, musculoskeletal pain, ophthalmic, or respiratory effects); at each visit
  • Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version


back to top
 
J - Administrative Information

Approximate Patient Visit
CYCLDOCE
2 hours
CYCLDOCE+TRAS
First cycle: 3.5 hours; Subsequent cycles: 2.5 hours
Pharmacy Workload (average time per visit)
CYCLDOCE
38.085 minutes
CYCLDOCE+TRAS
47.174 minutes
Nursing Workload (average time per visit)
CYCLDOCE
59.167 minutes
CYCLDOCE+TRAS
79.167 minutes
 
K - References

Jones S, Holmes FA, O’Shaughnessy JO, et al. Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of US oncology research trial 9735. JCO 2009; 27(8): 1177-83.

Jones SE, Mavin MA, Holmes FA et al. Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. JCO 2006; 24: 5381-7.

Cyclophosphamide, docetaxel, trastuzumab drug monographs, Cancer Care Ontario.


PEBC Advice Documents or Guidelines

December 2019 Updated NDFP form and biosimilar information in Drug Regimen and Drug Administration and Special Precautions sections.


back to top
 
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.