1. ¹1st Department of Pathology and Experimental Cancer Research, Semmelweis University and Molecular Pathology Research Group Joint Research Organisation of the Hungarian Academy of Sciences, and Semmelweis University Budapest, Hungary
2. ²Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Peptide Biochemistry Research Group Joint Research Organisation of the Hungarian Academy of Sciences and Semmelweis University Budapest, H-1085 Budapest, Üllõi u. 26, Hungary

Correspondence: Dr B Szende, E-mail: bszende@korb1.sote.hu

Received 30 April 2002; Revised 6 September 2002; Accepted 18 September 2002.

Abstract

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.