A Follow-up Assessment of Subjects Who Received Ganciclovir (Dihydroxypropoxymethyl Guanine [DHPG]) During the Phase I/II Study to Evaluate the Safety and Efficacy of Ganciclovir Treatment for Congenital Cytomegalovirus (CMV) Infections

Ganciclovir has been shown to be carcinogenic, teratogenic, and gonadal toxic in animal models. Mice treated with ganciclovir experienced an increase in the incidence of tumors of the preputial gland (males), harderian gland (males), forestomach (males and females), ovaries (females), uterus (females), mammary gland (females), clitoral gland (females), vagina (females), and liver (females). While the preputial and clitoral glands, forestomach, and harderian glands of mice do not have human counterparts, ganciclovir is considered a potential carcinogen in humans. Animal data indicate that administration of ganciclovir causes inhibition of spermatogenesis and subsequent infertility, possibly due to inhibition of rapidly dividing cell populations including spermatogonia. In the animal models, these effects were reversible at lower doses and irreversible at higher doses. In both male and female mice, ganciclovir has been shown to cause decreased fertility. Gonadal toxicity in rats, mice, and dogs included testicular atrophy in males and, more variable, ovarian atrophy in females. There are no data in humans that demonstrate these effects following treatment with ganciclovir. This study seeks to formally establish the overall sexual development, cancer incidence, and pubertal status of those study subjects who previously received six weeks of ganciclovir as they now approach puberty. The original study was performed from 1986 to 1991, and therefore subjects who were enrolled are now nine to fourteen years of age.