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

Trial Information

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.