Vincristine

 Risk Factor: DM
 Class: ANTINEOPLASTICS

Contents of this page:

Fetal Risk Summary
Breast Feeding Summary
References
Questions and Answers

Fetal Risk Summary


Vincristine is an antimitotic antineoplastic agent. The drug is embryocidal and teratogenic in mice, hamsters, and monkeys (1). Doses that produced these effects were nontoxic to the pregnant animal.

The use of vincristine has been described in at least 36 pregnancies (1 with twins), 9 during the 1st trimester (2,3,4,5,6,7,8,9,10,11,12, 13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30 and 31).

A mother with Hodgkin's disease treated with vincristine, vinblastine, and procarbazine in the 1st trimester (3 weeks after the last menstrual period) delivered a 1900-g male infant at about 37 weeks' gestation (10). Neonatal death occurred because of respiratory distress syndrome. At autopsy, a small secundum atrial septal defect was found. In a Hodgkin's case treated with vincristine, mechlorethamine, and procarbazine during the 1st trimester, the electively aborted fetus had malformed kidneys (markedly reduced size and malpositioned) (16). Other adverse fetal outcomes observed following vincristine use include a 1000-g male infant born with pancytopenia who was exposed to six different antineoplastic agents in the 3rd trimester (2) and transient severe bone marrow hypoplasia in another newborn that was most likely caused by mercaptopurine (19). Intrauterine fetal death occurred in a 1200-g female fetus 36 hours after maternal treatment with vincristine, doxorubicin, and prednisone for diffuse, undifferentiated lymphoma of T-cell origin at 31 weeks' gestation (22). The fetus was macerated, but no other abnormalities were observed at autopsy. 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 (25). Vincristine was administered 4 times between 2225 weeks' 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 (25).

A 1999 report from France described the outcomes of pregnancies in 20 women with breast cancer who were treated with antineoplastic agents (31). 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 (SABs) (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 (31). Vincristine (V), in combination with doxorubicin (D), epirubicin (E), and/or methotrexate (M), was administered to two women at a mean dose of 2 mg/m2. The outcomes were one SAB (VEM; exposed at 6 weeks' gestation) and one surviving liveborn infant (exposed to VD in the 2nd trimester) (31).

Data from one review indicated that 40% of the infants exposed to anticancer drugs were of low birth weight (32). This finding was not related to the timing of exposure. Long-term studies of growth and mental development in offspring exposed to these drugs during the 2nd trimester, the period of neuroblast multiplication, have not been conducted (33). However, individual infants have been evaluated for periods ranging from a few weeks up to 7 years and all have had normal growth and development (17,18,19 and 20, 22,23 and 24,26,27,29).

Vincristine, in combination with other antineoplastic agents, may produce gonadal dysfunction in men and women (34,35,36,37,38,39,40 and 41). Alkylating agents are the most frequent cause of this problem (38). Ovarian and testicular function may return to normal with successful pregnancies possible, depending on the patient's age at time of treatment and the total dose of chemotherapy received (34). In a 1989 case report, a woman with an immature teratoma of the ovary was treated with conservative surgery and chemotherapy consisting of six courses of vincristine, dactinomycin, and cyclophosphamide (42). She conceived 20 months after her last chemotherapy and eventually delivered a normal 3340-g male infant. The long-term effects of combination chemotherapy on menstrual and reproductive function have been described in a 1988 report (43). Twenty-nine of 40 women treated for malignant ovarian germ cell tumors received vincristine. The results of this study are discussed in the monograph for cyclophosphamide (see Cyclophosphamide).

In 436 long-term survivors treated with chemotherapy between 1958 and 1978 for gestational trophoblastic tumors, 132 (30%) received vincristine in combination with other antineoplastic agents (44). The mean duration of chemotherapy was 4 months with a mean interval from completion of therapy to the first pregnancy of 2.7 years. Conception occurred within 1 year of therapy completion in 45 women (antineoplastic agents used in these women were not specified), resulting in 31 live births, 1 anencephalic stillbirth, 7 SABs, and 6 elective abortions. Of the 132 women treated with vincristine, 37 (28%) had at least one live birth (numbers in parentheses refer to mean/maximum vincristine dose in milligrams) (7.4/17.0), 8 (6%) had no live births (7.1/22.0), 4 (3%) failed to conceive (7.3/18.0), and 83 (63%) did not try to conceive (11.3/46.0). The average ages at the end of treatment in the four groups were 24.9, 24.4, 24.4, and 31.5 years, respectively. Congenital abnormalities noted in the total group (368 conceptions) were two cases of anencephaly, and one case each of spina bifida, tetralogy of Fallot, talipes equinovarus, collapsed lung, umbilical hernia, desquamative fibrosing alveolitis, asymptomatic heart murmur, and mental retardation. Another child had tachycardia but developed normally after treatment. One case of sudden infant death syndrome occurred in a female infant at 4 weeks of age. None of these outcomes differed statistically from that expected in a normal population (44).

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 data are available.

References

  1. Product information. Oncovin. Eli Lilly, 2000.
  2. 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.
  3. 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.
  4. Daly H, McCann SR, Hanratty TD, Temperley IJ. Successful pregnancy during combination chemotherapy for Hodgkin's disease. Acta Haematol (Basel) 1980;64:1546.
  5. Tobias JS, Bloom HJG. Doxorubicin in pregnancy. Lancet 1980;1:776.
  6. Garcia V, San Miguel J, Borrasea AL. Doxorubicin in the first trimester of pregnancy. Ann Intern Med 1981;94:547.
  7. Dara P, Slater LM, Armentrout SA. Successful pregnancy during chemotherapy for acute leukemia. Cancer 1981;47:8456.
  8. Burnier AM. Discussion. In Plows CW. Acute myelomonocytic leukemia in pregnancy: report of a case. Am J Obstet Gynecol 1982;143:413.
  9. Lilleyman JS, Hill AS, Anderton KJ. Consequences of acute myelogenous leukemia in early pregnancy. Cancer 1977;40:13003.
  10. Thomas PRM, Peckham MJ. The investigation and management of Hodgkin's disease in the pregnant patient. Cancer 1976;38:144351.
  11. Pawliger DF, McLean FW, Noyes WD. Normal fetus after cytosine arabinoside therapy. Ann Intern Med 1971;74:1012.
  12. Lowenthal RM, Funnell CF, Hope DM, Stewart IG, Humphrey DC. Normal infant after combination chemotherapy including teniposide for Burkitt's lymphoma in pregnancy. Med Pediatr Oncol 1982;10:1659.
  13. Sears HF, Reid J. Granulocytic sarcoma: local presentation of a systemic disease. Cancer 1976;37:180813.
  14. Durie BGM, Giles HR. Successful treatment of acute leukemia during pregnancy: combination therapy in the third trimester. Arch Intern Med 1977;137:901.
  15. Newcomb M, Balducci L, Thigpen JT, Morrison FS. Acute leukemia in pregnancy: successful delivery after cytarabine and doxorubicin. JAMA 1978;239:26912.
  16. Mennuti MT, Shepard TH, Mellman WJ. Fetal renal malformation following treatment of Hodgkin's disease during pregnancy. Obstet Gynecol 1975;46:1946.
  17. Coopland AT, Friesen WJ, Galbraith PA. Acute leukemia in pregnancy. Am J Obstet Gynecol 1969;105:12889.
  18. Doney KC, Kraemer KG, Shepard TH. Combination chemotherapy for acute myelocytic leukemia during pregnancy: three case reports. Cancer Treat Rep 1979;63:36971.
  19. Okun DB, Groncy PK, Sieger L, Tanaka KR. Acute leukemia in pregnancy: transient neonatal myelosuppression after combination chemotherapy in the mother. Med Pediatr Oncol 1979;7:3159.
  20. Weed JC Jr, Roh RA, Mendenhall HW. Recurrent endodermal sinus tumor during pregnancy. Obstet Gynecol 1979;54:6536.
  21. Kim DS, Park MI. Maternal and fetal survival following surgery and chemotherapy of endodermal sinus tumor of the ovary during pregnancy: a case report. Obstet Gynecol 1989;73:5037.
  22. Karp GI, von Oeyen P, Valone F, Khetarpal VK, Israel M, Mayer RJ, Frigoletto FD, Garnick MB. Doxorubicin in pregnancy: possible transplacental passage. Cancer Treat Rep 1983;67:7737.
  23. Haerr RW, Pratt AT. Multiagent chemotherapy for sarcoma diagnosed during pregnancy. Cancer 1985;56:102833.
  24. Volkenandt M, Buchner T, Hiddemann W, Van De Loo J. Acute leukaemia during pregnancy. Lancet 1987;2:15212.
  25. Schleuning M, Clemm C. Chromosomal aberrations in a newborn whose mother received cytotoxic treatment during pregnancy. N Engl J Med 1987;317:16667.
  26. Feliu J, Juarez S, Ordonez A, Garcia-Paredes ML, Gonzalez-Baron M, Montero JM. Acute leukemia and pregnancy. Cancer 1988;61:5804.
  27. Turchi JJ, Villasis C. Anthracyclines in the treatment of malignancy in pregnancy. Cancer 1988;61:43540.
  28. Weinrach RS. Leukemia in pregnancy. Ariz Med 1972;29:3269.
  29. Ortega J. Multiple agent chemotherapy including bleomycin of non-Hodgkin's lymphoma during pregnancy. Cancer 1977;40:282935.
  30. Jones RT, Weinerman ER. MOPP (nitrogen mustard, vincristine, procarbazine, and prednisone) given during pregnancy. Obstet Gynecol 1979;54:4778.
  31. Giacalone PL, Laffargue F, Benos P. Chemotherapy for breast carcinoma during pregnancy. Cancer 1999;86:226672.
  32. Nicholson HO. Cytotoxic drugs in pregnancy: review of reported cases. J Obstet Gynaecol Br Commonw 1968;75:30712.
  33. Dobbing J. Pregnancy and leukaemia. Lancet 1977;1:1155.
  34. Schilsky RL, Sherins RJ, Hubbard SM, Wesley MN, Young RC, DeVita VT Jr. Long-term follow-up of ovarian function in women treated with MOPP chemotherapy for Hodgkin's disease. Am J Med 1981;71:5526.
  35. Schwartz PE, Vidone RA. Pregnancy following combination chemotherapy for a mixed germ cell tumor of the ovary. Gynecol Oncol 1981;12:3738.
  36. Estiu M. Successful pregnancy in leukaemia. Lancet 1977;1:433.
  37. Johnson SA, Goldman JM, Hawkins DF. Pregnancy after chemotherapy for Hodgkin's disease. Lancet 1979;2:93.
  38. Schilsky RL, Lewis BJ, Sherins RJ, Young RC. Gonadal dysfunction in patients receiving chemotherapy for cancer. Ann Intern Med 1980;93:10914.
  39. Sherins RJ, DeVita VT Jr. Effect of drug treatment for lymphoma on male reproductive capacity. Ann Intern Med 1973;79:21620.
  40. Sherins RJ, Olweny CLM, Ziegler JL. Gynecomastia and gonadal dysfunction in adolescent boys treated with combination chemotherapy for Hodgkin's disease. N Engl J Med 1978;299:126.
  41. Lendon PRM, Peckham MJ. The investigation and management of Hodgkin's disease in the pregnant patient. Cancer 1976;38:194451.
  42. Lee RB, Kelly J, Elg SA, Benson WL. Pregnancy following conservative surgery and adjunctive chemotherapy for stage III immature teratoma of the ovary. Obstet Gynecol 1989;73:8535.
  43. Gershenson DM. Menstrual and reproductive function after treatment with combination chemotherapy for malignant ovarian germ cell tumors. J Clin Oncol 1988;6:2705.
  44. Rustin GJS, Booth M, Dent J, Salt S, Rustin F, Bagshawe KD. Pregnancy after cytotoxic chemotherapy for gestational trophoblastic tumours. Br Med J 1984;288:1036.

Questions and Answers

alternatives to vincristine in ALL. My daughter has ALL and has developed a sever polycranial neuropathy?, has anyone had experience with this? Obviously , we are in close contact with her MD but I was looking for other parents or ALL survivors. She is grade 3 neuropathy. Can no longer walk or sit up. I have great fear of continuation of therapy using vincristine.

We usually defer the administration of Vincristine until all the signs of neuropathy have abated. Chemotherapy then proceeds as scheduled minus the Vincristine. I have just one question: Have you ruled out the possibility of CNS involvement by Leukemia?

why vincristine is most used cancer drug?, vincristine oncovo is mostly used cancer drug.what are its advantages over other chemotherapeutic agents.is it has less side effects or more therapeutic effects.

I had vincristine as part of CHOP.
A side effect I had was peripheral neuropathy. I didn't mind it that much because it sure beats cancer.

How do you extract vincristine/vinblastine from the Madagscar Periwinkle?,

There are used several methods:
Supercritical Fluid Extraction ( yield about 76% )
http://www.jstage.jst.go.jp/article/cpb/...

Use of an organ culture:
http://www.freepatentsonline.com/4831133...
http://www.actahort.org/books/447/447_29...

Extraction with solvent combined with semi-synthetic ( enzymatic ) production process:
http://209.85.135.104/search?q=cache:qHd...
http://www.freepatentsonline.com/4918011...
http://www3.interscience.wiley.com/cgi-b...

how can the chemo therapy drug Vincristine be harmful to the cells?, im doing an anatomy papper so any technical terms will be helpful :)
thanx

You can learn a lot about Vincristine by reading the drug insert (this is a PDF):

http://patient.cancerconsultants.com/dru...

A few other sites with sections on how Vincristine "works" (written more in layman's terms):

http://www.chemocare.com/bio/vincristine...

(scroll down towards the bottom of the page)

Also check out the "Mechanism of Action" section here:

http://www.merck.com/mmpe/lexicomp/vincr...

Hope it helps. Best of luck with you paper.

Vincristine is an anti cancer drug that works by proventing microtubules from disassembling.?, How does this property make it a good drug?

It's actually the opposite. Vincristine prevents ASSEMBLY of microtubules, thereby inhibiting the mitotic process of cells.

The basis behind a majority of chemotherapy drugs is to limit the growth of all rapidly dividing cells which includes cancer cells. Microtubule formation is essential for mitotic replication, and so the prevention of microtubule formation equates the inhibition of cancer cell proliferation...But it also leads to a lot of negative side-effects.

which active ingredient blastine or vincristine is more used in chemotherapy now a days?, vincristine & vinblastine are most used vinca alkaloids in preparation of drugs used in cancer treatment but one is more popular among pharmacist than other which is that

vincristine oncovin

How can Vincristine and Adriamycin (used to treat cancer) be fatal to a cell?,

Basically both drugs slow or stop the growth of cancer cells in the body. They are given together because each attacks the cells in a different way. Both drugs work on different parts of the cancer cell's life cycle, which increases the chance that more cancer cells are killed.

Vincristine is in a family of drugs known as antineoplastic medications. Antineoplastics can cause the death of cancer cells by interfering with the DNA, which is necessary for their growth and reproduction.

Adriamycin (also called Doxorubicin) is a anthracycline which is a subgroup to the antineoplastics. Adriamycin prevents the growth of cancer cells by interfering with DNA, which is necessary for reproduction of cells.

Used together and in combinations these powerful drugs treat the following cancers:
breast cancer, ovarian cancer., bladder cancer , lung cancer, thyroid cancer, gastric cancer, soft tissue and osteogenic sarcomas, acute myeloblastic leukemia, acute lymphoblastic leukemia, Hodgkin's disease, non-Hodgkin's lymphomas, neuroblastoma, rhabdomyosarcoma, Wilms' tumor, Kaposi's sarcoma

Medline Plus: Vincristine
http://www.nlm.nih.gov/medlineplus/drugi...

Medline Plus: Doxirubicin
http://www.nlm.nih.gov/medlineplus/drugi...

Could anyone help me with detailed information about vincristine and its anticancer effect?,

Contact the American Cancer Society. There is a good amount of research that is directly funded by them. Furthermore, they are on the cutting edge of cancer related research and information.

why does the drug vincristine have side effects such as loss of dividing cells an nerve problems?,

Vincristine
Trade Names: Oncovin В®, Vincasar Pfs В®
Other Names: Vincristine Sulfate, LCR, VCR

Drug Type:

Vincristine is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug. Vincristine is classified as a plant alkaloid.

What Vincristine Is Used For:

Cancers treated with Vincristine include: acute leukemia, Hodgkin's and non- Hodgkin's lymphoma, neuroblastoma, rhabdomyosarcoma, Ewing's sarcoma, Wilms' tumor, multiple myeloma, chronic leukemias, thyroid cancer, brain tumors.
It is also used to treat some blood disorders.


Side effects may include:
Taste changes
Peripheral neuropathy: Although uncommon, a serious side effect of decreased sensation and paresthesia (numbness and tingling of the hands and feet) may be noted. Sensory loss, numbness and tingling, and difficulty in walking may last for at least as long as therapy is continued

How Vincristine Works:

Cancerous tumors are characterized by cell division, which is no longer controlled as it is in normal tissue. "Normal" cells stop dividing when they come into contact with like cells, a mechanism known as contact inhibition. Cancerous cells lose this ability. Cancer cells no longer have the normal checks and balances in place that control and limit cell division. The process of cell division, whether normal or cancerous cells, is through the cell cycle. The cell cycle goes from the resting phase, through active growing phases, and then to mitosis (division).

The ability of chemotherapy to kill cancer cells depends on its ability to halt cell division. Usually, the drugs work by damaging the RNA or DNA that tells the cell how to copy itself in division. If the cells are unable to divide, they die. The faster the cells are dividing, the more likely it is that chemotherapy will kill the cells, causing the tumor to shrink. They also induce cell suicide (self-death or apoptosis).

Chemotherapy drugs that affect cells only when they are dividing are called cell-cycle specific. Chemotherapy drugs that affect cells when they are at rest are called cell-cycle non-specific. The scheduling of chemotherapy is set based on the type of cells, rate at which they divide, and the time at which a given drug is likely to be effective. This is why chemotherapy is typically given in cycles.

Chemotherapy is most effective at killing cells that are rapidly dividing. Unfortunately, chemotherapy does not know the difference between the cancerous cells and the normal cells. The "normal" cells will grow back and be healthy but in the meantime, side effects occur. The "normal" cells most commonly affected by chemotherapy are the blood cells, the cells in the mouth, stomach and bowel, and the hair follicles; resulting in low blood counts, mouth sores, nausea, diarrhea, and/or hair loss. Different drugs may affect different parts of the body.

Vincristine belongs to a class of chemotherapy drugs called plant alkaloids. Plant alkaloids are made from plants. The vinca alkaloids are made from the periwinkle plant (catharanthus rosea). The taxanes are made from the bark of the Pacific Yew tree (taxus). The vinca alkaloids and taxanes are also known as antimicrotubule agents. The podophyllotoxins are derived from the May Apple plant. Camptothecan analogs are derived from the Asian "Happy Tree" (Camptotheca acuminata). Podophyllotoxins and camptothecan analogs are also known as topoisomerase inhibitors. The plant alkaloids are cell-cycle specific. This means they attack the cells during various phases of division.

does any one know about vascular tumors in infants and treating them with a drug called vincristine?,

I don't know about the disease itself but Vincristine my daughter had for a yr. She had it every Monday for a yr At the time she was 4 yrs old (she is now 15) and weighed around or less than 23 pounds......(due to her illness). This particular Chemo, (from asking older children on the floor and my own) most often makes your legs tingle or cramp, and also your stomach has some discomfort. It also leaves a metalicey taste in your mouth. Doctors usually have patients walk down a hall to monitor any problems walking as tendons can draw up. My daughters did not. I only know of one child on the floors who's did. My daughter did fine with this Chemo at top doseage.

I am not sure what your after but I hope this helps you. I do not know about your child's illness in particular or its history in shrinking this particular type of tumor, but I can tell you this is a common chemo in treatments for many things. For the effects.. I often asked older children on the floor their effects of the meds. Don't ask adults how it effected them, as children react differently. Ask older kids who are old enough to explain it. They were always happy to help out when ever I was asking.

You can also do an internet search and if you type it in in different ways it will bring different info sometimes. Such as type tumors, tumor's and such. Also take a peek at themiraclekids.com (If you want contact me 'll share which is my daughter). I think you might enjoy the site. Hugs and God Bless your child! Think POSSITIVE!



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