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.