Epirubicin

 Risk Factor: DM
 Class: ANTINEOPLASTICS

Contents of this page:

Fetal Risk Summary
Breast Feeding Summary
References
Questions and Answers

Fetal Risk Summary

Epirubicin is a cell cycle phase non-specific anthracycline in the same antineoplastic class as daunorubicin, doxorubicin, idarubicin, and valrubicin. It is used as adjuvant therapy in patients with breast cancer. The mechanism of action includes the inhibition of nucleic acid (DNA and RNA), protein synthesis, and DNA helicase activity.

In reproduction studies, epirubicin was embryolethal (increased resorptions and post-implantation loss) in pregnant rats administered an IV dose about 0.04 times the maximum recommended single human dose on a body surface basis (MRHD) during days 5 to 15 of gestation (1). Intrauterine growth retardation (IUGR), but not teratogenicity, was also observed up to this dose. Doses as low as 0.005 times the MRHD resulted in embryolethality, and IUGR was evident at a dose 0.0015 times the MRHD. At a dose approximately 2.5 times the MRHD given on days 9 and 10 of gestation, fetal deaths, reduced placental weight, and multiple congenital malformations (external: anal atresia, misshapen tail, abnormal genital tubercle; visceral: gastrointestinal, urinary, and cardiovascular systems; skeletal: deformed long bones and girdles, rib abnormalities, irregular spinal ossification) were observed (1). In contrast, a dose 0.02 times the MRHD during days 6 to 18 of gestation in rabbits was not embryotoxic or teratogenic (1). Administration of maternally toxic doses in rabbits caused abortions and delayed ossification, but no teratogenicity. In fertility studies with male and female rats, mice, rabbits, and dogs, various low doses of epirubicin were associated with atrophy of the testes and epididymis, reduced spermatogenesis, or uterine atrophy (1).

It is not known if epirubicin crosses the placenta. The molecular weight (about 580) is low enough, however, that transfer to the human fetus should be expected.

The manufacturer's product information describes two human pregnancies in which epirubicin was administered (1). In the first case, a 34-year-old woman at 28 weeks' gestation, who was diagnosed with breast cancer, was treated with epirubicin and cyclophosphamide every 3 weeks for three cycles. The last dose was given at 34 weeks' gestation and she delivered a healthy baby 1 week later. No follow-up of the infant after birth was mentioned. The second case involved a 34-year-old woman with breast cancer metastatic to the liver who was randomized to the FEC-50 regimen (epirubicin, 5-fluorouracil, and cyclophosamide). She was removed from the study because of pregnancy, but the gestational age and number of doses received were not specified. The pregnancy ended with a spontaneous abortion (1).

A 30-year-old woman at about 25 weeks' gestation was treated with four courses of epirubicin (100 mg) and vincristine (2 mg) for non-Hodgkin's lymphoma (2). Prednisolone was also given during each treatment and then tapered. Her disease responded well to the therapy. Labor was induced at 34 weeks' gestation and she gave birth to a normal 2.32-Kg, 44.5-cm long female infant with Apgar scores of 8 at 1 and 5 minutes. The mother has remained in complete remission and her child appeared to be doing well at 4 years of age.

A 1996 report described the case of a 39-year-old woman with extensive metastatic breast cancer who had a unilateral mastectomy and axillary dissection at 29 weeks' gestation (3). After surgery, she was started on combination chemotherapy with epirubicin (50 mg/m2), 5-fluorouracil (600 mg/m2), and cyclophosphamide (600 mg/m2). At 35 weeks' gestation, a few days after receiving her second course of therapy, she developed eclamptic tonic-clonic seizures. She subsequently delivered a healthy but growth-retarded (1650-g; <10th percentile) infant. Although hypertension and proteinuria were not detected before the seizures, both were documented in the postpartum period. No follow-up of the infant after delivery was reported.

A 1999 report from France described the outcomes of pregnancies in 20 women with breast cancer who were treated with antineoplastic agents (4). The first cycle of chemotherapy occurred at a mean gestational age of 26 weeks with delivery occurring at a mean 34.7 weeks. A total of 38 cycles were administered during pregnancy with a median of two cycles per woman. None of the women received radiation therapy during pregnancy. The pregnancy outcomes included two spontaneous abortions (SAB) (both exposed in the 1st trimester), one intrauterine death (exposed in the 2nd trimester), and 17 live births, one of whom died at 8 days of age without apparent cause. The 16 surviving children were developing normally at a mean follow-up of 42.3 months (4). Epirubicin (E), in combination with various other agents (cyclophosphamide [C], fluorouracil [F], methotrexate [M], or vincristine [V]) was administered to 10 of the women at a mean dose of 70 mg/m2 (range 50100 mg/m2). The outcomes were two SAB (ECF, EMV; 1st trimester), one stillbirth (one cycle of EC at 23 weeks'), one neonatal death (one cycle of ECF 32 days before birth), and six surviving liveborn infants (one EC, five ECF; all in the 3rd trimester). One of the infants, exposed to two cycles of ECF with the last at 25 days before birth, had transient leukopenia (4).

Occupational exposure of the mother to antineoplastic agents during pregnancy may present a risk to the fetus. A position statement from the National Study Commission on Cytotoxic Exposure and a research article involving some antineoplastic agents are presented in the monograph for cyclophosphamide (see Cyclophosphamide).

Breast Feeding Summary

No reports describing the use of epirubicin during human lactation have been located. The antineoplastic agent is excreted into the milk of lactating rats receiving 0.5 mg/kg/day (2). The molecular weight (about 580) is low enough that excretion into breast milk should be expected. In addition, another anthracycline (see Doxorubicin) is excreted into human milk. Because of the potential for serious adverse effects, such as immune suppression, carcinogenesis, neutropenia, and unknown effects on growth, women receiving epirubicin should not breast feed.

References

1. Product information. Ellence. Pharmacia & Upjohn, 2001.
2. Goldwasser F, Pico JL, Cerrina J, Fernandez H, Pons JC, Cosset JM, Hayat M. Successful chemotherapy including epirubicin in a pregnant non-Hodgkin's lymphoma patient. Leuk Lymphoma 1995;20:1736.
3. Muller T, Hofmann J, Steck T. Eclampsia after polychemotherapy for nodal-positive breast cancer during pregnancy. Eur J Obstet Gynecol Reprod Biol 1996;67:1978.
4. Giacalone PL, Laffargue F, Benos P. Chemotherapy for breast carcinoma during pregnancy. Cancer 1999;86:226672.
   
   

Questions and Answers

how is epirubicin made?, I would like to know how are the following drugs use in chemotherapy made: epirubicin,Citabine,taxol

They are mixed in special labs. One I know of is a company called Baxter. Maybe there is a website for them that may tell you?

How long after you finished chemo for breast cancer till your periods are regular?, Last Febuary (2006) I finished chemo for breast cancer I took the following chemos:
Brand Generic
Ellence epirubicin
Cytoxan cyclophosphamide
Adrucil 5-Fu, fluorouracil
Taxotere docetaxel
Xeloda capecitabine
Platinol cisplatin
Vepecid,VP16 etoposide
Avastin bevacizumab

How long might it take for my cycles to become regular?

As stated, everyone is different...

I had bc 2x and the first time I had

Cytoxin
Oh geesh, I forget the name now..Its also known as the RED DEVIL
and something else mixed in there..

It was 9 mos

The 2nd time I had
Xeloda and something else (sorry...) can't remember and it was like 8 mos.

GB

hope you are doing okay..I am so far :)