Epirubicin 90 / Cyclophosphamide 600, Breast Cancer, adjuvant

Protocol-ID: 579 V1.1 (Short), EC (EPIR90/CYCL600), Breast Ca, adj.

Indication(s)

Breast Cancer; ICD-10 C50.-

Protocol classification

Classification: alternative
Intensity: Standard dose
Therapy phase:
Therapy intention: curative

Cycles

Cycle length 21 days, recommended cycles: 4

Protocol sequences

Risks

Emetogenicity (MASCC/ESMO): moderate (30-90%)
Neutropenia: very high (>41%)
Febrile Neutropenia: intermediate (10-20%)
Thrombocytopenia below 50 000/µl: low (<10%)
Anemia Hb below 8g/dl: low (<5%)
Dyspnea: CTC AE °3-4: 5%

Therapy

Day	Substance	Dosage	Appl.	Inf. time	Procedure
HYD Hydration: Balanced Crystalloid Solution
Access: peripheral venous
Hydration before, during, or after antitumor therapy
1	Balanced Crystalloid Solution	500 ml	i.v.	30 min	30 min before Epirubicin (d1)

Day	Substance	Dosage	Solution	Appl.	Inf. time	Procedure
AE Antiemesis: Emetogenicity high (AC), FOSAP, GRAN i.v., DEXA i.v
Access: peripheral venous
DGHO 2016, DKG 2016, MASCC/ESMO 2016, on combinations of anthracycline and cyclophosphamide
1	Fosaprepitant	150 mg	NaCl 0.9% 150 ml	i.v.	20 min	30 min before Epirubicin (d1)
1	Dexamethasone	12 mg	NaCl 0.9% 50 ml	i.v.	5 min	30 min before Epirubicin (d1)
1	Granisetron	1 mg	NaCl 0.9% 50 ml	i.v.	5 min	15 min before Epirubicin (d1)
or other 5-HT3 receptor antagonist

Day	Substance	Dosage	Appl.	Inf. time	Procedure
SUP Supportive therapy: Mesna i.v., hour 0 (pre), p.o. 2 h, 6 h after onset Cyclophosphamide
Access: peripheral venous
Mesna 0h,2h,6h, prophylaxis of urinary tract toxicity by cyclophosphamide. At the time of oxazaphosphorin injection, 20% of the oxazaphosphorin dose is injected simultaneously as mesna. 2 and 6 h after onset, oral intake of 40% of the oxazaphosporin dose.
1	Mesna	120 mg/m² BSA	i.v.	1 min	1 min before Cyclophosphamide (d1)
1	Mesna	240 mg/m² BSA	p.o.		90 min after Cyclophosphamide (d1)
1	Mesna	240 mg/m² BSA	p.o.		5 h after Cyclophosphamide (d1)
It is to be taken 6 hours after the start of the cyclophosphamide infusion.

Day	Substance	Dosage	Solution	Appl.	Inf. time	Procedure
CTX Antineoplastic therapy: EPIR/CYCL Breast Carcinoma (EC)
Access: central venous, port
1	Epirubicin	90 mg/m² BSA	Dextrose 5% 500 ml	i.v.	45 min	Sequence
1	Cyclophosphamide	600 mg/m² BSA	NaCl 0.9% 500 ml	i.v.	30 min	Sequence

Day	Substance	Dosage	Appl.	Inf. time	Procedure
HW Hematopoietic growth factors: FN risk 10-20%, G-CSF long-acting, pegylated
Access: - none -
Risk of febrile neutropenia (FN) 10-20% and 1 risk factor: age > 65 y, laboratory parameters (anemia, lymphocytopenia < 700/µl, hypalbuminemia, hyperbilirubinemia) previous chemotherapy, comorbidities, low performance status, advanced symptomatic tumor disease (DKG 2016)
2	Pegfilgrastim	6 mg	subc	Bolus	24 h after Cyclophosphamide (d1)
Use at risk: FN 10-20% and 1 risk factor, other long-acting G-CSF possible.

Warnings

Epirubicin: cardiac toxicity, maximum cumulative dose 900-1000 mg/m² KOF. For EPIR extravasation: dry cold (not just before or after Dexrazoxane infusion) on day of extravasation. Dexrazoxane i.v. for 3 days: 2 days 1000 mg/m², 3rd day 500 mg/m², do not use in parallel with DMSO. First infusion as soon as possible and within the first 6 hours.

References

Sparano JA, Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med 2008 Apr 17;358(16):1663-71. doi: 10.1056/NEJMoa0707056. PMID: 18420499. [PMID]
von Minckwitz G, Capecitabine in addition to anthracycline- and taxane-based neoadjuvant treatment in patients with primary breast cancer: phase III GeparQuattro study. J Clin Oncol 2010 Apr 20;28(12):2015-23. doi: 10.1200/JCO.2009.23.8303. PMID: 20308671. [PMID]
De Laurentiis M, Taxane-based combinations as adjuvant chemotherapy of early breast cancer: a meta-analysis of randomized trials. J Clin Oncol 2008 Jan 01;26(1):44-53. doi: 10.1200/JCO.2007.11.3787. PMID: 18165639. [PMID]
Smith LA, Cardiotoxicity of anthracycline agents for the treatment of cancer: systematic review and meta-analysis of randomised controlled trials. BMC Cancer 2010 Jun 29;10:337. doi: 10.1186/1471-2407-10-337. PMID: 20587042. [PMID]
Khasraw M, Epirubicin: is it like doxorubicin in breast cancer? A clinical review. Breast 2012 Apr;21(2):142-9. doi: 10.1016/j.breast.2011.12.012. PMID: 22260846. [PMID]
Jones RL, A randomised pilot Phase II study of doxorubicin and cyclophosphamide (AC) or epirubicin and cyclophosphamide (EC) given 2 weekly with pegfilgrastim (accelerated) vs 3 weekly (standard) for women with early breast cancer. Br J Cancer 2009 Jan 27;100(2):305-10. doi: 10.1038/sj.bjc.6604862. PMID: 19165198. [PMID]

Recommendations

12/2023: European Society for Medical Oncology

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Valid since: 18.09.2023