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Anti‐tumor activity of CPT‐11 in experimental human ovarian cancer and human soft‐tissue sarcoma
Author(s) -
Jansen Willy J.M.,
Kolfschoten Geertruida M.,
Erkelens Caroline A.M.,
Van ArkOtte Jannette,
Pinedo Herbert M.,
Boven Epie
Publication year - 1997
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19971210)73:6<891::aid-ijc22>3.0.co;2-6
Subject(s) - sarcoma , ovarian cancer , topoisomerase , camptothecin , soft tissue sarcoma , cancer , growth inhibition , osteosarcoma , medicine , cancer research , pharmacology , biology , cell culture , oncology , pathology , enzyme , biochemistry , genetics
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 ×5 schedule than the weekly ×2 schedule, although a 2‐fold higher dose was administered in the weekly ×2 schedule. Since i.p. and i.v. injections were similarly effective, the selected treatment schedule was 20 mg/kg i.p. daily ×5, starting when tumors measured approximately 150 mm 3 . Growth inhibition of ≥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. Int. J. Cancer 73:891–896, 1997. © 1997 Wiley‐Liss, Inc.