Cancer in Pregnancy: Procarbazine

Procarbazine is a methylhydrazine derivative. It is used mostly in combination chemotherapy for the treatment of Hodgkinís disease and other lymphomas.

	Setting	Treatment	Outcomes
	Species studied
Animal studies *	Rats and mice ¹	5 ñ 10 mg/kg	Tail, appendicular, central nervous system, eye and jaw defects and cleft palate.
	Rats ¹	125 mg/kg	Neurogenic tumors in the offspring of treated rats
	Rat ²	1-10 mg/kg	Dose related reduction in fetal brain weight
	Rabbit ¹		Mandible and limb malformations
	Study design
Human studies	Case reports	1st trim exposure	There are at least 6 case reports of procarbazine exposure during the first trimester. Only two resulted in completely normal babies ^{3, 4} The following malformed infants were reported:
		vinblastine + procarbazine + vincristine	1. A 1900g male infant delivered at 37 weeks of pregnancy. He died after respiratory distress syndrome and at autopsy a small secundum atrial septal defect was observed ⁵.
		vincristine + nitrogen mustard + prednisone + procarbazine	2. A male fetus electively aborted with malpositioned kidneys with markedly reduced size. Karyotype performed on amniotic fluid cell culture was normal. ⁶
		Nitrogen mustard + vinblastine + procarbazine	3. A spontaneously aborted male fetus at 24 weeks of gestation, with only four toes in both feet and partial syndactyly ⁷
		Procarbazine alone from 11 wks before conception to 5 wks after	4. A normal male infant with an erythematous haemangioma measuring 2 X 0.5 cm on the forearm and several small round haemangiomas on the trunk and extremities. The baby was well after a 13 month follow-up ⁸. OBS: Two other malformed children were reported in case series and will be described below ^9,10.
		2nd and 3rd trim exposures	No abnormalities have been described after 2nd or 3rd trimester exposure to procarbazine. One woman who mistakenly took 50 mg of procarbazine daily for 30 days during the 2nd trimester of pregnancy, delivered a normal male baby ¹¹.
	Case series		No epidemiological studies of congenital anomalies among the infants of women treated with procarbazine during pregnancy were located. The following case series were located: 1. No congenital anomalies were observed in one series among 6 children born to women treated during pregnancy with cancer chemotherapeutic regimens that included procarbazine. Only one of these women was treated during the first trimester ¹². Their growth, intellectual development and cytogenetic analysis were normal in ages ranging from 3 - 19 years at time of the follow-up. 2. In a series of 26 pregnancies of women receiving chemotherapy for cancer there was one baby with cleft lip and palate who was exposed to lomustine, vincristine, prednisone and procarbazine from week 1- 6 and to vinblastine from week 9 to term ⁹. 3. In a case series of 13 patients with first trimester exposure to cancer chemotherapy, 3 were exposed to combination regimens, which included procarbazine. One pregnancy ended as a spontaneous abortion, one was electively terminated, and the last was a baby born with hydrocephalus, who died 4 hours after birth ¹⁰.

* - None of the animal studies reported in this table were conducted at The Hospital for Sick Children, Toronto, or by Motherisk.

References

Schardein JL. Chemically induced birth defects, Marcel Dekker, New York and Basel 1993, p 480.
Johnson JM et al: The effect of prenatal procarbazine treatment on brain development in the rat. Teratology 32:203-212, 1985.
Schapira DV, Cludley AD: Successful pregnancy following continous treatment with combination chemoterapy before conception and throughout pregnancy. Cancer 54:800-3, 1984.
Daly H et al: Successful pregnancy during combination chemotherapy for Hodgkinís disease. Acta Hematol (Basel) 64:154-6, 1980.
Thomas, P.R.M.; Peckham, M.J. The investigation and management of Hodgin's disease in the pregnant patient. Cancer 38: 1443-51, 1976.
Mennuti, M.T.; Shepard, T.H.; Mellman, W.J. Fetal renal malformation following treatment of Hodgkin's disease during pregnancy. Obstet Gynecol 46: 194-196, 1975.
Garett MJ: Teratogenic effects of combination chemoterapy. Ann Intern Med 80:667, 1974.
Wells JH et al: Procarbazine therapy for Hodgkinís disease in early pregnancy. J Am Med Assoc 205:935-7, 1968.
Mulvihill JJ et al: Pregnancy outcome in cancer patients. Cancer 60:1143-50, 1987.
Zemlickis D, Lishner M, Degendorfer P, et al. Fetal outcome after in utero exposure to cancer chemotherapy. Arch Intern Med. 152:573-576, 1992.
Daw EG: Procarbazine in pregnancy. Lancet 2: 984, 1970.
Aviles A, Diaz-Maqueo JC, Talavera A,et al. Growth and development of children of mothers treated with chemotherapy during pregnancy. Current status of 43 children. Am JHematol. 36: 243-248, 1991.
Schilsky RL et al: Long-term follow-up of ovarian function in women treated with MOPP chemotherapy for Hodgkinís disease. Cancer 52:988-93, 1983.
Viviani s et al: Gonadal toxicity after combination chemotherapy for Hodgkinís disease: comparative results of MOPP versus ABVD. Eur J Cancer Clin Oncol 21: 601-5, 1985.

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