Anti-tumor activity of CPT-11 in experimental human ovarian cancer and human soft-tissue sarcoma
Autor: | W J, Jansen, G M, Kolfschoten, C A, Erkelens, J, Van Ark-Otte, H M, Pinedo, E, Boven |
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Rok vydání: | 1997 |
Předmět: |
Ovarian Neoplasms
Mice Nude Sarcoma Irinotecan Antineoplastic Agents Phytogenic Mice DNA Topoisomerases Type I Injections Intravenous Tumor Cells Cultured Animals Humans Camptothecin Female RNA Messenger Sarcoma Experimental Drug Screening Assays Antitumor Injections Intraperitoneal Neoplasm Transplantation |
Zdroj: | International journal of cancer. 73(6) |
ISSN: | 0020-7136 |
Popis: | CPT-11, a semi-synthetic derivative of camptothecin, was investigated for its activity in panels of 15 human ovarian-cancer lines and 10 human soft-tissue sarcoma lines grown s.c. in nude mice. Various factors were analyzed that may be of influence on the extent of tumor-growth inhibition induced by CPT-11. At equitoxic doses, CPT-11 was more effective in the daily x5 schedule than the weekly x2 schedule, although a 2-fold higher dose was administered in the weekly x2 schedule. Since i.p. and i.v. injections were similarly effective, the selected treatment schedule was 20 mg/kg i.p. daily x5, starting when tumors measured approximately 150 mm3. Growth inhibition ofor = 75% was obtained in 8/15 human ovarian-cancer lines and in 6/10 human soft-tissue sarcoma lines. A weak correlation was found between topoisomerase-I mRNA in xenograft tissues and sensitivity to CPT-11. Relative topoisomerase-I expression was highest in MRI-H-207 and WLS-160 xenografts, in which CPT-11 was able to induce cures of all tumors. The high efficacy in the 2 panels of human tumor lines suggests over-prediction of its potential clinical activity in these tumor types. The difference in efficacy of CPT-11 between species may be related to the metabolism of the drug, since CPT-11 is converted more efficiently into SN-38 in mice. In addition, mice may be less sensitive to SN-38-induced side-effects. On the basis of the preclinical data, frequent administration of lower doses of CPT-11 should be considered in order to increase response rates in the clinic. |
Databáze: | OpenAIRE |
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