Cancer in Pregnancy: Pentostatin

Pentostatin (Deoxycoformycin; Covidarabine) is a potent non-competitive inhibitor of adenosine deaminase. Pentostatin is used in the treatment of lymphoproliferative malignancies, particularly hairy cell leukemia.

	Setting	Treatment	Outcomes
	Species studied
Animal studies *	mouse	5 mg/kg	In mice the mode of action is via abnormal development of the allantois ¹. Using 5 mg/kg on day 7, defects of neural tube closure and arch development were found on day 10 and followed by a high rate of embryonic loss ²
	rabbit	up to 0.02 mg/kg daily.	In the rabbit fetal toxicity occurred after intravenous administration but no teratogenicity ³. Fuchigami et al (1991) gave up to 0.1 mg/kg intravenously and found fetal death and toxicity at 0.02 mg per kg but no teratogenicity. ⁴
	rats	0.75 mg/kg	In rats fetal resorptions were increased and body weight reduced along with skeletal abnormalities and defects ³.
	mice	up to 1 mg/kg	Deficiency in spleen and thymus weight has been noted after perinatal treatment of mice with deoxycoformycin ⁵. All pups from dams treated during the last 5 days of pregnancy with deoxycoformycin died within 2 days of birth; however, treatment during embryogenesis had no effect on pup survival.
	Study Design
Human studies			No epidemiological studies of congenital anomalies in infants born towomen treated with dacarbazine during pregnancy have been reported.

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

References

Airhart, M.J.; Robbins, C.M.; Knudsen,T.B.; Church, J.K. and Skalko, R.G.: Developing allantois is a primarysite of 2'-deoxxycoformycin toxicity. Teratology 53:361-373, 1996.
Airhart, M.J.; Robbins, C.M.; Knudsen, T.B.; Church, J.K. and Skalko, R.G.: Occurrence of embryotoxicity in mouse embryos following in utero exposure to 2'-deoxycoformycin (pentostatin). Teratology 47:17-27,1993.
Dostal, L.A.; Brown, S.; Bleck, J. andAnderson, J.A.: Developmental toxicity of pentostatin (2'-deoxycoformycin) in rats and rabbits. Teratology 44:325-334, 1991.
Fuchigami, K.; Sameshima, K.; Izumi, H.;Honda, H.; Yamauchi, M.; Hayashida, M.; Inoue, H.; Kuwata, S.; Umehashi, M. and Shigaki, T.: Study by intravenous administration of YK-176 during the period of organogenesis in rabbits. The Clinical Report 25:4319-4327, 1991.
Luebke RW et al: Immune function in mice exposed to the adenosine deaminase inhibitor 2'-deoxycoformin during immune system development. Immunopharmacol Immunotoxicol 9:149-61, 1987.

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