A novel
somatostatin analogue,
TT-232 (which inhibits the proliferation of various cell cultures and transplantable mouse tumours), was examined regarding its effect on human
melanoma and
lymphoma xenografts as a single treatment or in combination with
DTIC (
dacarbazine) and
etoposide.
TT-232 inhibited the growth of HT-18
melanoma xenografts, a dose of 5 mg kg(-1) being the most effective. Combination of 1 mg kg(-1)
TT-232 with 30 or 60 mg kg(-1)
DTIC (administered daily) resulted in a stronger inhibitory effect compared to
TT-232 or
DTIC as a single modality. Antimetastatic effect of
TT-232 treatment combined with
DTIC was studied using the B16 mouse
melanoma muscle - lung
metastasis model. The number of lung
metastases of
B16 melanoma could be decreased by the daily administration of 1 mg kg(-1)
TT-232 or 60 mg kg(-1), but not of 30 mg kg(-1)
DTIC.
TT-232, combined with 30 or 60 mg kg(-1)
DTIC decreased the lung
metastasis number significantly lower than the control. Nearly 50% growth inhibition of HT-58
lymphoma was achieved by daily treatment with 1 mg kg(-1)
TT-232. 5 mg kg(-1)
etoposide, administered daily, resulted in a similar effect. The combination of 1 mg kg(-1)
TT-232 and 5 mg kg(-1)
etoposide was significantly more effective than
TT-232 or
etoposide as a single treatment. The very strong tumour growth inhibitory effect of 10 mg kg(-1)
etoposide could even be increased by combination with
TT-232. These experimental data suggest that
TT-232 may be an effective new tool in the
combination chemotherapy of malignant tumours like
melanoma and
lymphoma.