Reports on HIV/AIDS: 1990

JANUARY 26, 1990, MMWR, Vol. 39, RR-1: [inclusive page numbers]
APPENDIX I
Results of Studies Conducted by the
Burroughs-Wellcome Company of
Zidovudine Carcinogenicity Involving Animals
In lifetime carcinogenicity bioassays, mice and rats were given various doses of
zidovudine, up to the maximum tolerated doses, for most of their lifespans. Dose
reductions were necessary for both species during the study because of the onset and
persistence of drug-related anemia. Mice were treated initially with 30, 60, or 120
mg/kg/day; after 90 days, these doses were reduced to 20, 30, or 40 mg/kg/day,
respectively. Rats were treated initially with 80, 220, or 600 mg/kg/day; after 90 days,
the 600-mg/kg/day group was reduced to 450 mg/kg/day; and after 280 days, this
group was further reduced to 300 mg/kg/day. Although anemia persisted at the
reduced doses, drug treatment did not adversely affect survival in either species.
Among mice dosed for approximately 22 months, seven vaginal neoplasms
occurred in 60 female animals at the highest dose. The earliest a tumor was
discovered was after 19 months of continuous dosing; most tumors were discovered
after 21 months of treatment. The tumors consisted of five nonmetastasizing
squamous cell carcinomas and two benign tumors (one squamous cell papilloma and
one squamous cell polyp). One benign vaginal tumor (squamous cell papilloma) was
discovered in the middle-dose group after 22 months of treatment. In all instances,
these lesions were discovered during histologic examination of tissues from animals
that either died or were sacrificed, late in life from nontreatment-related causes, or
sacrificed upon completion of lifetime dosing.
Among rats dosed for approximately 22 months, two nonmetastasizing vaginal
squamous cell carcinomas were diagnosed on the basis of histologic examination of
tissues from animals receiving the highest dose. These carcinomas were discovered
after 20-22 months of dosing. No vaginal tumors occurred among rats given the
middle or low dose.
No other drug-related tumors were observed among animals of either sex or of
either species (Burroughs-Wellcome Company [letter to physicians], Dec. 5, 1989).

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