Preclinical and clinical trials of topoisomerase inhibitors.

CPT-11, developed by Yakult Honsha, has achieved the position of standard chemotherapy for colorectal cancer in the United States and in Western countries because CPT-11 + 5FU + LV showed survival benefit compared with 5FU-LV in two randomized controlled trials. CPT-11 has been distributed to almost all countries. In Japan, combination therapy of CDDP + CPT-11 was significantly superior to CDDP-VP-16 in the treatment of extensive disease small cell lung cancer. This combination is also active against non-small cell lung cancer. Daiich Pharmaceutical Co. developed a more active nonmasked form of camptothecin derivative, DX-8915f. The phase I study of a new camptothecin inhibitor, DX-8915f, has just been completed. The new topoisomerase I inhibitors of indolocarbazol derivatives, NB-506 and J107088, developed by Banyu Co., have strong antitumor activity and a wide therapeutic ratio. The phase I trial of J107088 is currently ongoing in the United States and Japan. These do not show any cross-resistance to MDR drugs.