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.
Saijo
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National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan. nsaijo@gan2.res.ncc.go.jp
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D018288:Carcinoma, Small Cell / Q000188:drug therapy; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy; D059004:Topoisomerase I Inhibitors
D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D059004:Topoisomerase I Inhibitors; D000077146:Irinotecan; C095887:exatecan; D002166:Camptothecin