A PHASE-II TRIAL OF DAUNOXOME, LIPOSOME-ENCAPSULATED DAUNORUBICIN, INPATIENTS WITH METASTATIC ADENOCARCINOMA OF THE COLON

Context. Liposomal encapsulation of drugs can potentially ameliorate t oxicities and improve acute and chronic tolerance. The increased uptak e of liposomes by colon adenocarcinoma cell lines may enable DaunoXome to circumvent the p-glycoprotein-mediated anthracycline resistance of colon cancer cells. Purpose, To determine if DaunoXome, liposome-enca psulated daunorubicin, has clinical activity in patients with adenocar cinoma of the colon who failed treatment with a 5-fluorouracil contain ing regimen. Method: In a Phase II trial, patients with metastatic ade nocarcinoma of the colon, whose disease has progressed after receiving one 5-fluorouracil-containing regimen, were treated with DaunoXome 10 0 mg/m(2) repeated every 3 weeks. Results: In this trial 16 patients r eceived 45 courses of therapy. No objective tumor responses were seen. Hematologic toxicities consisted of neutropenia (grade 3 and 4), grad e 2 anemia, and grade 2 thrombocytopenia. Nonhematologic toxicities we re mild and manageable. Of the 16 patients, 5 experienced hushing, sho rtness of breath, chest tightness, and back pain during DaunoXome infu sion, which resolved with infusion interruption, diphenhydramine, and meperidine. Conclusions: DaunoXome is generally well tolerated at a do se of 100 mg/m(2) every 3 weeks. Toxicities are mild and reversible. O n this schedule DaunoXome does not have significant clinical activity in patients with metastatic adenocarcinoma of the colon who have progr essed after one 5-fluorouracil-containing regimen.