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

Context. Liposomal encapsulation of drugs can potentially ameliorate toxicities and improve acute and chronic tolerance. The increased uptake 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-encapsulated daunorubicin, has clinical activity in patients with adenocarcinoma of the colon who failed treatment with a 5-fluorouracil containing regimen. Method: In a Phase II trial, patients with metastatic adenocarcinoma of the colon, whose disease has progressed after receiving one 5-fluorouracil-containing regimen, were treated with DaunoXome 100 mg/m(2) repeated every 3 weeks. Results: In this trial 16 patients received 45 courses of therapy. No objective tumor responses were seen. Hematologic toxicities consisted of neutropenia (grade 3 and 4), grade 2 anemia, and grade 2 thrombocytopenia. Nonhematologic toxicities were mild and manageable. Of the 16 patients, 5 experienced hushing, shortness of breath, chest tightness, and back pain during DaunoXome infusion, which resolved with infusion interruption, diphenhydramine, and meperidine. Conclusions: DaunoXome is generally well tolerated at a dose of 100 mg/m(2) every 3 weeks. Toxicities are mild and reversible. On this schedule DaunoXome does not have significant clinical activity in patients with metastatic adenocarcinoma of the colon who have progressed after one 5-fluorouracil-containing regimen.