Preclinical and clinical trials of topoisomerase inhibitors

Ann N Y Acad Sci. 2000;922:92-9. doi: 10.1111/j.1749-6632.2000.tb07028.x.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Antineoplastic Agents, Phytogenic / adverse effects
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Camptothecin / administration & dosage
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives*
  • Camptothecin / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Small Cell / drug therapy
  • Clinical Trials as Topic
  • Colorectal Neoplasms / drug therapy
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / therapeutic use*
  • Humans
  • Irinotecan
  • Lung Neoplasms / drug therapy
  • Topoisomerase I Inhibitors*

Substances

  • Antineoplastic Agents, Phytogenic
  • Enzyme Inhibitors
  • Topoisomerase I Inhibitors
  • Irinotecan
  • exatecan
  • Camptothecin