Diflomotecan, a promising homocamptothecin for cancer therapy.

Abstract

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.

• Authors: Judith R Kroep, Hans Gelderblom
• Journal: Expert opinion on investigational drugs (Expert Opin Investig Drugs) Vol. 18 Issue 1 Pg. 69-75 (Jan 2009) ISSN: 1744-7658 [Electronic] England
• PMID: 19053883 (Publication Type: Journal Article, Review)

Chemical References

• diflomotecan
• Camptothecin

Topics

• Animals
• Camptothecin (adverse effects, analogs & derivatives, chemistry, pharmacokinetics, therapeutic use)
• Clinical Trials as Topic
• Humans
• Neoplasms (drug therapy)
• Treatment Outcome