NEW YORKHigh-dose liposome-encapsulated daunorubicin(Drug information on daunorubicin) (DaunoXome) with G-CSF support appears promising in solid tumors, a team led by George D. Demetri, MD, of Dana-Farber Cancer Institute, reported at the Chemotherapy Foundation Symposium.
Patients were stratified by prior an-thracycline therapy. Patient cohorts (each with at least 3 patients) were treated with at least two cycles of DaunoXome at 140, 180, 225, and 250 mg/m². Individual patients were treated at one assigned dose level; no intrapatient dose reductions or escalations were permitted.
DaunoXome was administered in an outpatient setting by 2-hour intravenous infusion. G-CSF injection was begun the day after chemotherapeutic administration and continued until the patients recovery from neutropenia nadir.
A total of 27 patients had been enrolled in the study as of June 1998. Dr. Anthony Elias, reporting on behalf of the research team, said that, to date, no patient has experienced clinically significant mucositis or exhibited hand-foot syndrome. Grade 4 neutropenia was common on all dose levels, but was transient. No grade 4 thrombocytopenia was seen, and uncomplicated febrile neutropenia occurred in only 9 of 59 cycles. Dose-limiting cardiotoxicity was noted in two patients treated at 225 mg/m2 following cumulative anthracycline doses of 450 and 675 mg/m².
Dr. Elias said that pharmacokinetic analysis showed the expected increase in AUC of daunorubicin and daunorubicinol, as well as decreases in clearance and volume of distribution, compared with unencapsulated anthracycline.
Because dose-limiting cardiotoxicity was noted with repetitive dosing at 225 mg/m², accrual at 180 mg/m² is being expanded as a potential phase II dose level. Intensive dosing with single-agent DaunoXome is a promising approach for integrating anthracycline into sequential high-dose-drug delivery strategies with acceptable tolerance, he concluded.