4-Demethoxydaunorubicin (4-DMDR), an anthracydine analogue available in i.v. and p.o. form, has shown significant antitumor activity in murine tumor models while produdng less cardiac toxidty than doxorubidn at equimyelotoxic doses. Phase I and clinical pharmacology studies of the i.v. and p.o. preparation were performed. With i.v. 4-DMDR, consistent myelosuppression was observed at a dose of 15 mg/sq m at a median Day 15; mild nausea and vomiting were observed in 9% of all treatment courses. In patients given p.o. 4-DMDR, myelosuppression occurred at median Day 14 in 10 of 12 patients given 50 mg/sq m. Nausea and vomiting occurred in 25% of all treatment courses, and dividing the dose over 3 days did not decrease the inddence. Alopecia occurred in 13% of evaluable patients treated with the i.v. preparation and 30% of evaluable patients treated p.o. No stomatitis was observed with either preparation, and no patient developed clinical signs of congestive heart failure. Pharmacokinetic studies were performed with both preparations and revealed prolonged plasma levels of the 13-hydroxy metabolite 4-DMDR-ol. The suggested starting dose for Phase II studies is 12.5 mg/sq m given every 21 days for i.v. 4-DMDR with dose escalation by 2.5 mg/sq m in the absence of myelotoxidty. For p.o. 4-DMDR, the suggested starting dose is 40 mg/sq m given every 21 days with escalation by 10 mg/sq m if no myelotoxidty is observed.
|Original language||English (US)|
|Number of pages||6|
|State||Published - Dec 1 1983|
ASJC Scopus subject areas
- Cancer Research