Diflomotecan, a promising homocamptothecin for cancer therapy.
Diflomotecan, a 10,11-difluoro-homocamptothecin, represents a new promising class of topoisomerase I inhibitors with enhanced plasma stability and superior preclinical anti-tumour activity as compared to the established camptothecins, irinotecan and topotecan. Diflomotecan was the first homocamptothecin to enter clinical studies. Phase I data are summarized for both the intravenous and oral schedules. The toxicity is primarily haematological while no severe gastrointestinal toxicity has been observed in contrast to other topoisomerase I inhibitors. Diflomotecan has a high oral bioavailability (72 - 95%) and the oral day 1 - 5 every 3 weeks regimen is recommended for Phase II testing because it is relatively well tolerated, convenient and mimics protracted exposure. This review summarizes the developments and innovations in the topoisomerase I inhibitor field with an emphasis on diflomotecan.
Kroep
Judith R
JR
Leiden University Medical Center, Department of Clinical Oncology, PO Box 9600, K1-P, 2300RC, Leiden, The Netherlands. j.r.kroep@lumc.nl
Gelderblom
Hans
H
D000818:Animals; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome
C424962:diflomotecan; D002166:Camptothecin