Background Cidofovir [(S)-1-(3-hydroxy-2-phosphonyl-methoxypropyl) cytosine
] is a commercially available nucleotide analogue that has antiviral activi
ty against a broad range of DNA viruses and is effective against human cyto
megalovirus infection.
Objectives We aimed to study the effect of cidofovir on growth of the highl
y aggressive melanoma tumour arising from mouse melanoma B16 cells grafted
subcutaneously in C57B16/J mice.
Methods Mice were treated daily with systemic cidofovir at several doses. I
n treated and control groups, tumour growth was measured using a calliper,
and histological studies were performed.
Results In untreated mice, massive invasive melanoma tumours were observed
on day 5 after tumour cell grafting. Cidofovir treatment gave a dose-depend
ent reduction in tumour size. Tumour growth was inhibited by 62% at a dose
of 37.5 mg kg(-1) three times weekly, as compared with control mice treated
with saline alone. At 67 mg kg(-1) three times weekly, tumour growth was i
nhibited by 90%. Increasing the cidofovir dose to 50 or 100 mg kg(-1) daily
resulted in a gradual increase in the antitumoral effect of the compound.
In one experiment, cidofovir was administered at 100 mg kg(-1) five times w
eekly from the eighth day after the injection of tumour cells, when the tum
our already had a volume of approximately 100 mm(3). In the treatment group
, on the 14th day the tumour volume was approximately 200 mm(3), while in t
he control group it had increased to 750 mm(3).
Conclusions Although the mechanism is unknown, an antitumoral or antiangiog
enic effect may be the reason for the activity of cidofovir in this model.
In view of our findings, use of cidofovir should be further explored in the
treatment of neoplastic diseases.