Thalidomide was recently suggested to be an angiogenesis-inhibitor fol
lowing the demonstration of its activity in a rabbit cornea micropocke
t model. The purpose of the present study was to test its efficacy in
solid tumors in mice. B16-F10 melanoma and CT-26 colon carcinoma cells
were injected subcutaneously, intravenously and intraperitoneally, an
d mice received daily gavage of 0.3-1.0 mg thalidomide starting either
two or 10 days following tumor cell injection. The tumors were measur
ed and compared with controls. There was to growth retardation in CT-2
6 bearing mice nor in mice with pulmonary or peritoneal metastases of
B16-F10 melanoma. In 3/7 groups of mice with SC B16-F10 tumors, growth
retardation was demonstrated, however the difference was not statisti
cally significant. All tumors eventually reached maximal size, similar
to controls. Morphological evaluation of the blood vessels oriented t
owards the tumor revealed that in both thalidomide and control groups,
all mice had developed an intact network of new blood vessels. In our
model for the oral administration of thalidomide inhibition of tumor
growth and angiogenesis did not occur. We hypothesize that the lack of
sustained antiangiogenic response was either due to immune modulation
or to tumor heterogeneity and adaptation.