Epirubicin 90 / Cyclophosphamide 600, Breast Cancer, adjuvant

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

• EC (EPIR90/CYCL600), Breast Ca, adj. (PID579) -|- PACL80, Breast Ca, adj. (PID581)
• Neoadjuvant WSG-TP-II (Paclitaxel)
• Neoadjuvant WSG-TP-II (Letrozole)
• Neoadjuvant WSG-TP-II (Tamoxifen) -|- PERT840/TRAS8/TMXF20, Breast Ca, adj., C1 (PID2450)

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

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.

Notes

This protocol was established based on a recommendation from the AGO to extrapolate from AC + paclitaxel to EC + paclitaxel and use in dose equivalent because of the more favorable side effect profile. In the work of Smith and Khasraw, the lower cardiotoxicity of EPIR vs DOXO is addressed. The side effect profile was based on the publication by Minckwitz for EC followed by docetaxel.

Cycles

Cycle length 21 days, recommended cycles: 4

Controls:

• Blood count: on day 1 and subsequently weekly
• ECG Cardiotoxicity of epirubicin, check cardiac function before/under therapy recommended. See technical info
• Day 1: GOT, GPT, GGT, Bilirubin, AP, Cholinesterase Epirubicin: continuous liver monitoring is necessary during therapy. In case of elevated bilirubin, dose adjustment, if necessary, see summary of product characteristics. Cyclophosphamide: dose reduction is recommended in case of impaired liver function.
• Day 1: Creatinine, glomerular filtration rate (GFR) Epirubicin: If serum creatinine levels are elevated (> 5 mg/dl), the dose should be reduced. Cyclophosphamide: In case of impaired renal function, dose reduction is recommended.
• Day 1: Urine status Urinary sediment must be checked regularly for erythrocytes and other signs of uro/nephrotoxicity.
• Day 1: Na⁺, K⁺, Ca²⁺, Mg²⁺ Cyclophosphamide: exclusion of electrolyte disturbances before use.

Pharmacokinetics

Epirubicin: hepatischer Abbau, 50% biliäre Elimination Cyclophosphamid: hepatischer Abbau, hauptsächlich renale Elimination

Original indication

Paclitaxel weekly, Breast Cancer, adjuvant

Original author

Sparano JA (2008)

Origin

The Eastern Cooperative Oncology Group, Southwest Oncology Group, Cancer and Leukemia Group, Noth Central Cancer Treatment Group

References

• Sparano JA, Weekly paclitaxel in the adjuvant treatment of breast cancer., N Engl J Med 2008 Apr 17;358(16):1663-71 [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 [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 1;26(1):44-53 [PMID]
• Smith LA, Cardiotoxicity of anthracycline agents for the treatment of cancer: systematic review and meta-analysis of randomised controlled trials., BMC Cancer 2010;10:337 [PMID]
• Khasraw M, Epirubicin: is it like doxorubicin in breast cancer? A clinical review., Breast 2012 Apr;21(2):142-9 [PMID]

Recommendations

• 08/2019: European Society for Medical Oncology
• 03/2023: National Comprehensive Cancer Network

Status

Valid since 2023-09-18, Version 1.1, last updated 2023-09-09

Last modification: V1.1: Protocol name changed according to current standard V1.0: Cato test successful. Use this scheme for first 4 cycles, then use protocol EC x 4 followed by PACL, Breast Ca, adj., B. V0.1: Cyclophosphamide duration and sequence according to primary literature. Epirubicin duration is according to carrier solution volume.

Important notice

The copyrighted protocols are treatment recommendations. The information contained in this compilation on cytostatic drugs, concomitant medication and other therapeutic procedures, as well as dosage and application information, is continuously reviewed with all due care by the authors and editors involved. Nevertheless, the publishers and authors do not assume any liability for the correctness - also with regard to possible printing errors.

The protocols may not be changed in terms of content.

Diagnosis, indication for therapy and treatment of malignant diseases must be carried out in each individual case by the hematologist and oncologist on his or her own responsibility. The treating physician is obligated to this personal responsibility to weigh in each case before a diagnostic or therapeutic measure, indication, contraindications, dosage and application under consideration of the specialized information or other documents of the manufacturers. This applies in particular to rarely used preparations or preparations that are new to the market.

The publishers and authors assume no liability for the accuracy of the contents. The application is at the own responsibility of the treating physician. ©Onkopti.