Cytarabine

 Risk Factor: DM
 Class: ANTINEOPLASTICS

Contents of this page:

Fetal Risk Summary
Breast Feeding Summary
References
Questions and Answers

Fetal Risk Summary

Cytarabine is an antineoplastic agent used in the treatment of various types of leukemia. The drug is teratogenic in the hamster and rat (1).

Normal infants have resulted following in utero exposure to cytarabine during all stages of gestation (2,3,4,5,6,7,8,9,10, 11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26 and 27). Follow-up of seven infants exposed in utero during the 2nd trimester to cytarabine revealed normal infants at 460 months (20,22,23,24,25 and 26). Two cases of intrauterine fetal death after cytarabine combination treatment have been located (20,23). In one case, maternal treatment for 5 weeks starting at the 15th week of gestation ended in intrauterine death at 20 weeks' gestation of a fetus without abnormalities or leukemic infiltration (20). The second case also involved a woman treated from the 15th week who developed severe pregnancy-induced hypertension at 29 weeks' gestation (23). An apparently normal fetus died 1 week later, most likely as a consequence of the preeclampsia.

Use during the 1st and 2nd trimesters has been associated with congenital and chromosomal abnormalities (21,28,29 and 30). One leukemic patient treated during the 2nd trimester elected to have an abortion at 24 weeks' gestation (21). The fetus had trisomy for group C autosomes without mosaicism. A second pregnancy in the same patient with identical therapy ended normally. In another case, a 34-year-old woman with acute lymphoblastic leukemia was treated with multiple antineoplastic agents from 22 weeks' gestation until delivery of a healthy female infant 18 weeks later (28). Cytarabine was administered only during the 27th week of gestation. Chromosomal analysis of the newborn revealed a normal karyotype (46,XX) but with gaps and a ring chromosome. The clinical significance of these findings is unknown, but because these abnormalities may persist for several years, the potential existed for an increased risk of cancer as well as for a risk of genetic damage in the next generation (28). Two women, one treated during the 1st trimester and the other treated throughout pregnancy, delivered infants with multiple anomalies: Bilateral microtia and atresia of external auditory canals, right hand lobster claw with three digits, bilateral lower imb defects (29) Two medial digits of both feet missing, distal phalanges of both thumbs missing with hypoplastic remnant of the right thumb (30) Congenital anomalies have also been observed after paternal use of cytarabine plus other antineoplastics prior to conception (31). The investigators suggested that the antineoplastic agents may have damaged the sperm without producing infertility in the two fathers. The relationship between use of the chemotherapy in these men and the defects observed is doubtful due to the lack of experimental evidence and confirming reports. The results of these pregnancies were: tetralogy of Fallot, syndactyly of first and second digits of right foot, and a stillborn with anencephaly. Cytarabine may produce reversible azoospermia (32,33). However, male fertility has been demonstrated during maintenance therapy with cytarabine (34).

Pancytopenia was observed in a 1000-g male infant exposed to cytarabine and five other antineoplastic agents during the 3rd trimester (12).

Data from one review indicated that 40% of the mothers exposed to antineoplastic drugs during pregnancy delivered low-birth-weight infants (35). This finding was not related to the timing of exposure. Except for the few cases noted above, long-term studies of growth and mental development in offspring exposed to cytarabine during the 2nd trimester, the period of neuroblast multiplication, have not been conducted (36).

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 cytarabine during lactation have been located. Because of the potential for serious adverse effects in nursing infants, women receiving this drug should not breast feed.

References

1. Product information. Cytosar-U. Pharmacia & Upjohn, 2000.
2. Pawliger DF, McLean FW, Noyes WD. Normal fetus after cytosine arabinoside therapy. Ann Intern Med 1971;74:1012.
3. Au-Yong R, Collins P, Young JA. Acute myeloblastic leukemia during pregnancy. Br Med J 1972;4:4934.
4. Raich PC, Curet LB. Treatment of acute leukemia during pregnancy. Cancer 1975;36:8612.
5. Gokal R, Durrant J, Baum JD, Bennett MJ. Successful pregnancy in acute monocytic leukaemia. Br J Cancer 1976;34:299302.
6. Sears HF, Reid J. Granulocytic sarcoma: local presentation of a systemic disease. Cancer 1976;37:180813.
7. Durie BGM, Giles HR. Successful treatment of acute leukemia during pregnancy. Arch Intern Med 1977;137:901.
8. Lilleyman JS, Hill AS, Anderton KJ. Consequences of acute myelogenous leukemia in early pregnancy. Cancer 1977;40:13003.
9. Moreno H, Castleberry RP, McCann WP. Cytosine arabinoside and 6-thioguanine in the treatment of childhood acute myeloblastic leukemia. Cancer 1977;40:9981004.
10. Newcomb M, Balducci L, Thigpen JT, Morrison FS. Acute leukemia in pregnancy: successful delivery after cytarabine and doxorubicin. JAMA 1978;239:26912.
11. Manoharan A, Leyden MJ. Acute non-lymphocytic leukaemia in the third trimester of pregnancy. Aust N-Z J Med 1979;9:714.
12. Pizzuto J, Aviles A, Noriega L, Niz J, Morales M, Romero F. Treatment of acute leukemia during pregnancy: presentation of nine cases. Cancer Treat Rep 1980;64:67983.
13. Colbert N, Najman A, Gorin NC, Blum F, Treisser A, Lasfargues G, Cloup M, Barrat H, Duhamel G. Acute leukaemia during pregnancy: favourable course of pregnancy in two patients treated with cytosine arabinoside and anthracyclines. Nouv Presse Med 1980;9:1758.
14. Tobias JS, Bloom HJG. Doxorubicin in pregnancy. Lancet 1980;1:776.
15. Taylor G, Blom J. Acute leukemia during pregnancy. South Med J 1980;73:13145.
16. Dara P, Slater LM, Armentrout SA. Successful pregnancy during chemotherapy for acute leukemia. Cancer 1981;47:8456.
17. Plows CW. Acute myelomonocytic leukemia in pregnancy: report of a case. Am J Obstet Gynecol 1982;143:413.
18. De Souza JJL, Bezwoda WR, Jetham D, Sonnendecker EWW. Acute leukaemia in pregnancy: a case report and discussion on modern management. S Afr Med J 1982;62:2956.
19. Feliu J, Juarez S, Ordonez A, Garcia-Paredes ML, Gonzalez-Baron M, Montero JM. Acute leukemia and pregnancy. Cancer 1988;61:5804.
20. Volkenandt M, Buchner T, Hiddemann W, Van De Loo J. Acute leukaemia during pregnancy. Lancet 1987;2:15212.
21. Maurer LH, Forcier RJ, McIntyre OR, Benirschke K. Fetal group C trisomy after cytosine arabinoside and thioguanine. Ann Intern Med 1971;75:80910.
22. Lowenthal RM, Marsden KA, Newman NM, Baikie MJ, Campbell SN. Normal infant after treatment of acute myeloid leukaemia in pregnancy with daunorubicin. Aust N-Z J Med 1978;8:4312.
23. O'Donnell R, Costigan C, O'Donnell LG. Two cases of acute leukaemia in pregnancy. Acta Haematol 1979;61:298300.
24. Doney KC, Kraemer KG, Shepard TH. Combination chemotherapy for acute myelocytic leukemia during pregnancy: three case reports. Cancer Treat Rep 1979;63:36971.
25. Cantini E, Yanes B. Acute myelogenous leukemia in pregnancy. South Med J 1984;77:10502.
26. Alegre A, Chunchurreta R, Rodrigueq-Alarcon J, Cruz E, Prada M. Successful pregnancy in acute promyelocytic leukemia. Cancer 1982;49:1523.
27. Hamer JW, Beard MEJ, Duff GB. Pregnancy complicated by acute myeloid leukaemia. N-Z Med J 1979;89:2123.
28. Schleuning M, Clemm C. Chromosomal aberrations in a newborn whose mother received cytotoxic treatment during pregnancy. N Engl J Med 1987;317:16667.
29. Wagner VM, Hill JS, Weaver D, Baehner RL. Congenital abnormalities in baby born to cytarabine treated mother. Lancet 1980;2:989.
30. Schafer AI. Teratogenic effects of antileukemic chemotherapy. Arch Intern Med 1981;141:5145.
31. Russell JA, Powles RL, Oliver RTD. Conception and congenital abnormalities after chemotherapy of acute myelogenous leukaemia in two men. Br Med J 1976;1:1508.
32. Lendon M, Palmer MK, Hann IM, Shalet SM, Jones PHM. Testicular histology after combination chemotherapy in childhood for acute lymphoblastic leukaemia. Lancet 1978;2:43941.
33. Lilleyman JS. Male fertility after successful chemotherapy for lymphoblastic leukaemia. Lancet 1979;2:1125.
34. Matthews JH, Wood JK. Male fertility during chemotherapy for acute leukemia. N Engl J Med 1980;303:1235.
35. Nicholson HO. Cytotoxic drugs in pregnancy: review of reported cases. J Obstet Gynaecol Br Commonw 1968;75:30712.
36. Dobbing J. Pregnancy and leukaemia. Lancet 1977;1:1155.
    
    

Questions and Answers

Where does Cytarabine come from?, I am doing a project for Marine Biology, and apparently it comes from a marine organism. Anyone know if this is true?

The drug was isolated from the Caribbean sponge Cryptotheca crypta.

http://www.futurepharm.com

How could the hemogloblin count go up during chemotherapy?, I got some results that show that as a patient was getting chemotherapy (Daunorubicin and Cytarabine), the amoutn of white blood cells and platelets went down, but the mass of hemogloblin per Liter went up. Anybody able to explain this?

Possible that the patient being treated with a red blood cell booster drug like Arnasep or Procrit? (i.e. EPO.)

My hemoglobin was ridiculously low at diagnosis for advanced stage Hodgkin's Disease -- it was actually around 7.0. So I started getting Arnasep shots and it increased despite the chemo. Once it hit 11.0, the Arnasep was discontinued, but my hemoglobin still kept climbing despite the chemo. If the patient was like me and had a heavy disease burden, perhaps knocking back the cancer is allowing the body and bone marrow to function better.

Would also consider dehydration -- makes the blood more concentrated which can make the hemoglobin level seem higher.

ARA-C/Cytarabine question?, Can anyone tell me anything about ARA-C. I will ask my son's oncologist all about it when he goes in on Tuesday but I'd like to be prepared. I would especially like to hear from people who have had this med or know someone who has and I'd like to know your individual reactions to this medication.

I have aml and was treated with this in the high dose form. The ara c did not cause me to loose my hair, but it did cause horrible skin reactions. It was almost like I was burnt from the inside out. My whole body was red, and it burned but was itchy at the same time. It was horrible. THey treated the reaction iwth attarax and different creams. It did cause a lot of nausea for me, but really, skin reaction was the worst.

what is cytarabine used for? (it is a drug)?,

Cytarabine is used to help treat certain types of leukemia's.

Cytarabine is also used to treat non-Hodgkin's lymphomato

Cytarabine belongs a group of drugs known as antimetabolites. It resembles a normal cell nutrient needed by cancer cells to grow.
The cancer cells take up cytarabine, which then interferes with their growth.

It can be taken either by injection in a vein under the skin of the forearm or in some cases injected into the spinal cord

Check with your Dr before taking any meds that is not prescribed to you