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Antitumor activity of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothec in, a novel water-soluble derivative of camptothecin, against murine tumors

Cancer Res. 1987 Nov 15;47(22):5944-7.

Abstract

The search for new water-soluble analogues of camptothecin (CPT) with higher activity and less toxicity has led to the development of a novel compound, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxy-camptothecin (CPT-11), which showed significant antitumor activity against a broad spectrum of experimental tumor models by i.p., i.v., or oral administration. When its activity against L1210 was compared with that of CPT and known derivatives, CPT-11 was most effective, giving the highest maximum increase in life span (ILS) and showing good activity over a wide dose range. The antitumor activity of CPT-11 was shown against tumors not only in the ascites form but also in the solid form. Included among the more susceptible murine tumors are S180, Meth A fibrosarcoma, Lewis lung carcinoma, Ehrlich carcinoma, MH134 hepatoma, mammary carcinoma of C3H/HeN mice, L1210, and P388 leukemia. Probable cures of these tumors were induced frequently by CPT-11. The antitumor activity of CPT-11 against i.p.-implanted L1210 was superior to that of Adriamycin in maximum ILS, the number of cured mice, and the therapeutic ratio. CPT-11 at a dose of 100 mg/kg produced an ILS in excess of 300% with five of six mice surviving tumor free, and effected 100% tumor regression at 200 mg/kg, whereas the optimum dose of Adriamycin, 12.5-25 mg/kg, brought about 114-129% ILS with one of six mice surviving. The acute toxicity of CPT-11 was extremely low, particularly in the case of oral administration. CPT-11 is expected to be clinically useful.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Camptothecin / analogs & derivatives*
  • Camptothecin / therapeutic use
  • Dose-Response Relationship, Drug
  • Irinotecan
  • Mice
  • Mice, Inbred Strains
  • Neoplasms, Experimental / drug therapy*

Substances

  • Antineoplastic Agents
  • Irinotecan
  • Camptothecin