Nedaplatin (NSC 375101D, NDP) is a derivative of cisplatin which produced less nausea & vomiting and nephrotoxicity. the effect of NDP on the 7-ethyl-1-hydroxy-CPT (the active form of CPT-11)-induced inhibitory effect on DNA topoisomerase I was examined. The topoisomerase I-inhibitory effect of 7-ethyl-1-hydroxy-CPT was enhanced 10-fold in the presence of Nedaplatin (NSC 375101D, NDP) at microgram/milliliter concentrations. Nedaplatin (NSC 375101D, NDP) was developed as a second generation platinum complex. Because it has greater antitumour activity and lower nephrotoxicity than cisplatin (CDDP). At the high-dose of Nedaplatin (NSC 375101D, NDP) in FN therapy, a reduction of tumour size and long-term tumour-free survival were frequently observed. The survival effect of the combinations of Nedaplatin (NSC 375101D, NDP) with 5-FU was superior to those of the combination of CDDP with 5-FU. In conclusion, the sequence-dependent antitumour efficacy and toxicity of the combination of NDP or CDDP with 5-FU was demonstrated in this study, and FN therapy appeared to be the most efficient regimen as a clinical therapy.