The NCCP Chemotherapy Regimen outlines the use of DOXOrubicin and Cyclophosphamide (AC 60/600) for the adjuvant treatment of high-risk breast cancer, administered every 21 days for four cycles. The document specifies dosing, eligibility criteria, exclusions, supportive care, and potential adverse effects, emphasizing the need for clinician discretion in treatment adjustments. It also includes guidelines for monitoring and managing complications associated with the chemotherapy regimen.
The NCCP Chemotherapy Regimen outlines the use of DOXOrubicin and Cyclophosphamide (AC 60/600) for the adjuvant treatment of high-risk breast cancer, administered every 21 days for four cycles. The document specifies dosing, eligibility criteria, exclusions, supportive care, and potential adverse effects, emphasizing the need for clinician discretion in treatment adjustments. It also includes guidelines for monitoring and managing complications associated with the chemotherapy regimen.
The NCCP Chemotherapy Regimen outlines the use of DOXOrubicin and Cyclophosphamide (AC 60/600) for the adjuvant treatment of high-risk breast cancer, administered every 21 days for four cycles. The document specifies dosing, eligibility criteria, exclusions, supportive care, and potential adverse effects, emphasizing the need for clinician discretion in treatment adjustments. It also includes guidelines for monitoring and managing complications associated with the chemotherapy regimen.
The NCCP Chemotherapy Regimen outlines the use of DOXOrubicin and Cyclophosphamide (AC 60/600) for the adjuvant treatment of high-risk breast cancer, administered every 21 days for four cycles. The document specifies dosing, eligibility criteria, exclusions, supportive care, and potential adverse effects, emphasizing the need for clinician discretion in treatment adjustments. It also includes guidelines for monitoring and managing complications associated with the chemotherapy regimen.
DOXOrubicin, and Cyclophosphamide (AC 60/600)Therapy
- 21 day INDICATIONS FOR USE: Regimen Reimbursement INDICATION ICD10 Code status Adjuvant treatment of high risk node negative or node C50 00252a Hospital positive breast cancer.
TREATMENT: The starting dose of the drugs detailed below may be adjusted downward by the prescribing clinician, using their independent medical judgement, to consider each patients individual clinical circumstances.
DOXOrubicin and cyclophosphamide are administered once every 21 days for four cycles (one cycle = 21 days). If radiation therapy is required, it is given following completion of chemotherapy.
Order of Day Drug Dose Route Diluent & Rate Cycle
Admin 1 1 DOXOrubicin 60mg/m2 IV push Slow IV push over Every 21 days 15min for up to 4 cycles 2 1 Cyclophosphamide 600mg/m2 IV infusion* 250ml 0.9% Every 21 days sodium chloride for up to 4 over 30min cycles * Cyclophosphamide may also be administered as an IV bolus over 5-10mins Lifetime cumulative dose of DOXOrubicin is 450mg/m2 In establishing the maximal cumulative dose of an anthracycline, consideration should be given to the risk factors outlined belowi and to the age of the patient.
Facilities to treat anaphylaxis MUST be present when the chemotherapy is administered.
ELIGIBILITY: Indications as above. ECOG status 0-2.
EXCLUSIONS: Hypersensitivity to DOXOrubicin, cyclophosphamide or any of the excipients. Congestive heart failure (LVEF < 50%) or other significant heart disease.
PRESCRIPTIVE AUTHORITY: The treatment plan must be initiated by a Consultant Medical Oncologist.
NCCP Protocol: AC (60-600) Published: 29/04/2015
Version number: 6 Therapy-21 day Review: 12/05/2026 Tumour Group: Breast ISMO Contributor: Prof Maccon Keane Page 1 of 4 NCCP Protocol Code: 00252 The information contained in this document is a statement of consensus of NCCP and ISMO or IHS professionals regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use of these documents is the responsibly of the prescribing clinician. and is subject to HSE’s terms of use available at http://www.hse.ie/eng/Disclaimer This information is valid only on the day of printing, for any updates please check www.hse.ie/NCCPchemoprotocols NCCP Chemotherapy Regimen
TESTS: Baseline tests: FBC, renal and liver profile. ECG MUGA or ECHO (LVEF > 50% to administer DOXOrubicin) if >65 years or if clinically indicated
Regular tests: FBC, renal and liver profile If clinically indicated creatinine, MUGA scan or echocardiogram
Disease monitoring: Disease monitoring should be in line with the patient’s treatment plan and any other test/s as directed by the supervising Consultant.
DOSE MODIFICATIONS: Any dose modification should be discussed with a Consultant
Haematological: Table 1: Dose modifications for cycles of DOXOrubicin and cyclophosphamide ANC (x109/L) Platelets (x109/L) Dose (Both Drugs) ≥ 1.5 > 90 100% 1 -1.49 70 to 90 *75% <1 < 70 Delay *May consider using G-CSF for neutrophil support rather than dose reduction
Renal and Hepatic Impairment:
Table 2: Dose modification of DOXOrubicin and Cyclophosphamide in Renal and hepatic impairment Drug Renal Impairment Hepatic Impairment DOXOrubicin No dose reduction required. Serum Bilirubin (micromol/L) Dose Clinical decision in severe 20-51 50% impairment 51-85 25% >85 Omit If AST 2-3 x normal give 75% If AST > 3 x ULN give 50% Cyclophosphamide CrCl (mL/min) Dose Severe impairment. Clinical Decision >20 100% 10-20 75% <10 50%
NCCP Protocol: AC (60-600) Published: 29/04/2015
Version number: 6 Therapy-21 day Review: 12/05/2026 Tumour Group: Breast ISMO Contributor: Prof Maccon Keane Page 2 of 4 NCCP Protocol Code: 00252 The information contained in this document is a statement of consensus of NCCP and ISMO or IHS professionals regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use of these documents is the responsibly of the prescribing clinician. and is subject to HSE’s terms of use available at http://www.hse.ie/eng/Disclaimer This information is valid only on the day of printing, for any updates please check www.hse.ie/NCCPchemoprotocols NCCP Chemotherapy Regimen
SUPPORTIVE CARE: EMETOGENIC POTENTIAL: DOXOrubicin: High (Refer to local policy) Cyclophosphamide: Moderate (Refer to local policy)
PREMEDICATIONS: None usually required
OTHER SUPPORTIVE CARE:
Prophylactic G-CSF may be used to mitigate the risk of haematological toxicities. Patients should have an increased fluid intake of 2-3 litres on day 1 to prevent haemorrhagic cystitis associated with cyclophosphamide.
ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS:
The adverse effects listed are not exhaustive. Please refer to the relevant Summary of Product Characteristics for full details. Neutropenia: Fever or other evidence of infection must be assessed promptly and treated appropriately. Extravasation: DOXOrubicin may cause pain and tissue necrosis if extravasated. (Refer to local extravasation guidelines). Cardiac Toxicity: DOXOrubicin is cardiotoxic and must be used with caution, if at all, in patients with severe hypertension or cardiac dysfunction.
DRUG INTERACTIONS: CYP3A inhibitors decrease the conversion of cyclophosphamide to both its active and inactive metabolites. Patients should also be counselled with regard to consumption of grapefruit juice. CYP3A inducers may also increase the conversion of cyclophosphamide to both its active and inactive metabolites. Concurrent administration of calcium channel blockers with DOXOrubicin should be avoided as they may decrease the clearance of DOXOrubicin. Current drug interaction databases should be consulted for more information.
REFERENCES: 1. Fisher, B et al. Treatment of axillary lymph node-negative, estrogen receptor-negative breast cancer: updated findings from National Surgical Adjuvant Breast and Bowel Project clinical trials. J Natl Cancer Inst 2004; 96 (24):1823 2. Fisher B, Brown AM, Dimitrov NV et al. Two months of doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with 6 months of cyclophosphamide, methotrexate and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: results from the National Surgical Adjuvant Breast and Bowel Project B-15. J Clin Oncol 1990;8(9):1483-96.
NCCP Protocol: AC (60-600) Published: 29/04/2015
Version number: 6 Therapy-21 day Review: 12/05/2026 Tumour Group: Breast ISMO Contributor: Prof Maccon Keane Page 3 of 4 NCCP Protocol Code: 00252 The information contained in this document is a statement of consensus of NCCP and ISMO or IHS professionals regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use of these documents is the responsibly of the prescribing clinician. and is subject to HSE’s terms of use available at http://www.hse.ie/eng/Disclaimer This information is valid only on the day of printing, for any updates please check www.hse.ie/NCCPchemoprotocols NCCP Chemotherapy Regimen
3. Doxorubicin 2mg/ml Concentrate for Solution for Infusion. Summary of Product Characteristics. Accessed April 2021. Available at: https://www.hpra.ie/img/uploaded/swedocuments/Licence_PA2315-083-001_26022020112618.pdf 4. Endoxana Injection 500mg Powder for Solution for Injection. Summary of Product Characteristics. Accessed April 2021. Available at: https://www.hpra.ie/img/uploaded/swedocuments/Licence_PA2299-027-001_21122018112107.pdf 5. Dosage Adjustment for Cytotoxics in Renal Impairment January 2009; North London Cancer Network. 6. Dosage Adjustment for Cytotoxics in Hepatic Impairment January 2009; North London Cancer Network. 7. NCCP Classification Document for Systemic Anti-Cancer Therapy (SACT) Induced Nausea and Vomiting. V3 2021. Available at: https://www.hse.ie/eng/services/list/5/cancer/profinfo/chemoprotocols/nccp-classification- document-for-systemic-anti-cancer-therapy-sact-induced-nausea-and-vomiting.pdf
Version Date Amendment Approved By
1 29/04/2015 Dr Maccon Keane 2 14/06/2017 Updated title, clarified administration Prof Maccon Keane order and dosing in renal and hepatic impairment, applied new NCCP regimen template 3 19/06/2019 Standardisation of treatment table for Prof Maccon Keane NCIS. 4 06/11/2019 Standardisation of treatment table Prof Maccon Keane 5 08/01/2020 Update of cyclophosphamide dose Prof Maccon Keane modifications in hepatic impairment 6 12/05/2021 Reviewed. Amended emetogenic Prof Maccon Keane potential.
Comments and feedback welcome at oncologydrugs@cancercontrol.ie.
i Cardiotoxicity is a risk associated with anthracycline therapy that may be manifested by early (acute) or late (delayed) effects. Risk factors for developing anthracycline-induced cardiotoxicity include: • high cumulative dose, previous therapy with other anthracyclines or anthracenediones • prior or concomitant radiotherapy to the mediastinal/pericardial area • pre-existing heart disease • concomitant use of other potentially cardiotoxic drugs In establishing the maximal cumulative dose of an anthracycline, consideration should be given to the risk factors above and to the age of the patient
NCCP Protocol: AC (60-600) Published: 29/04/2015
Version number: 6 Therapy-21 day Review: 12/05/2026 Tumour Group: Breast ISMO Contributor: Prof Maccon Keane Page 4 of 4 NCCP Protocol Code: 00252 The information contained in this document is a statement of consensus of NCCP and ISMO or IHS professionals regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. Use of these documents is the responsibly of the prescribing clinician. and is subject to HSE’s terms of use available at http://www.hse.ie/eng/Disclaimer This information is valid only on the day of printing, for any updates please check www.hse.ie/NCCPchemoprotocols
BC Cancer Protocol Summary For Primary Treatment of Visible Residual (Extreme Risk) Invasive Epithelial Ovarian, Fallopian Tube or Peritoneal Cancer Using Carboplatin and Paclitaxel
BC Cancer Protocol Summary For Primary Treatment of Visible Residual (Extreme Risk) Invasive Epithelial Ovarian, Fallopian Tube or Peritoneal Cancer Using Carboplatin and Paclitaxel
