Phase II trial of liposomal doxorubicin at 40 mg/m² every 4 weeks in endometrial carcinoma: A Gynecologic Oncology Group Study

Objective. In patients with disseminated endometrial carcinoma, liposomal doxorubicin has possible advantages over doxorubicin which has proven single agent activity but well known cardiac toxicity. Before replacing doxorubicin in clinical trials, the Gynecologic Oncology Group (GOG) decided to conduct a phase II clinical trial of liposomal doxorubicin (Ortho Biotech Products L. P., Raritan, NJ) in first-line therapy of patients with disseminated endometrial carcinoma. Methods. Patients with initial histologic confirmation of endometrial carcinoma presenting with disseminated or recurrent cancer who had not previously received cytotoxic drugs were considered for participation in this clinical trial. Eligible patients had measurable disease, GOG performance status 0-2, and adequate bone marrow, renal, and hepatic function according to standard criteria. Liposomal doxorubicin 40 mg/m² was given by intravenous injection on an every 4-week cycle until toxicity or progression. Patients who remained free from tumor progression or intolerable toxicity received at least one to a maximum of 20 cycles of liposomal doxorubicin. Results. Fifty-six patients were registered, of whom three were determined ineligible (prior malignancy = 2, inadequate pathology material = 1). One patient never received therapy, leaving 52 evaluable patients. Two patients (3.8%) achieved a complete response, four (7.7%) exhibited a partial response, and 31 (59.7%) had stable disease. The most common adverse events were constitutional (32/52), anemia (28/52), pain (27/52), dermatologic (25/52), and cardiovascular (12/52). Conclusions. In this trial, liposomal doxorubicin had a response rate of 11.5% in first-line treatment of disseminated endometrial carcinoma when given at 40 mg/m² every 4 weeks. In view of the associated skin toxicity at this dose, liposomal doxorubicin does not appear to be a suitable replacement for the more active doxorubicin for therapy of endometrial carcinoma.