PRECLINICAL ANTITUMOR-ACTIVITY OF ETHYLDESHYDROXYSPARSOMYCIN IN COMBINATION WITH CISPLATIN

The efficacy of cisplatin (CDDP) in combination with the protein synth esis inhibitor ethyldeshydroxysparsomycin (EDSM) has been tested in tw o tumor models at various schedules. Mice with L1210 leukemia or B16 m elanoma were treated with CDDP alone or in combination with EDSM. Agai nst L1210 leukemia, which is sensitive to CDDP, combinations elicited increases in life-span for all treatment schedules compared to those a chieved with the corresponding dose of CDDP. Moreover, the combination of EDSM with this platinum compound yielded a cure rate > 80%, compar ed to < 35% for single CDDP treatment. Although the B16 melanoma is ra ther resistant to both CDDP and EDSM, combinations of these agents aga inst B16 melanoma showed schedule dependent efficacy and in certain sc hedules significant therapeutic advantage over individual drug treatme nt, but cures were not observed. Our results suggest that EDSM has sig nificant synergistic capabilities in both animal tumor models, but str ong therapeutic enhancement of cisplatin efficacy is only seen when th e tumor is sensitive to CDDP.