Phase II study of liposomal doxorubicin in platinum- and paclitaxel-refractory epithelial ovarian cancer

Purpose: Stealth liposomal doxorubicin (Alzal Corp, Pale Alto, CA) has a sl ower clearance rate than free doxorubicin, resulting in sustained serum lev els. Liposomal encapsulation also leads to increased concentration of drug in tumor tissue. Meta-analysis of previous studies has shown that doxorubic in has activity in epithelial ovarian cancer. The current study was develop ed to examine the activity of Stealth liposomal doxorubicin in platinum- an d paclitaxel-refractory ovarian cancer. Patients and Methods: Patients had epithelial ovarian cancer that either pr ogressed on or recurred within 6 months of completion of platinum and pacli taxel chemotherapy. All patients had measurable disease. Stealth liposomal doxorubicin war administered at 50 mg/m(2) every 4 weeks as a 1 hour infusi on. Results: Eighty-nine patients were treated and in eluded in an intent to-tr eat analysis. There were 82 patients who were platinum and paclitaxel refra ctory and met all study criteria, There was one complete response and 14 pa rtial responses, for a total response rate of 16.9% (95% confidence interva l [CI], 9.1% to 24.6%). For platinum- and paclitaxel-refractory patients, t he response rate was 18.3% (95% CI, 9.9% to 26.7%), Median time to progress ion was 19.3 weeks for the entire population, Ten patients (11.2%) withdrew because of adverse events related to the drug (palmar-plantar erythrodyses thesia [PPE], n = 3; asthenia, n = 2; cardiac, n = 2; neutropenia, n = 1;st omatitis, n = 1; and edema, n = 1). There were no drug-related fatal events . There were only eight grade 4 adverse events attributable to the drug. St omatitis, PPE, and skin lesions were managed with dose reductions and delay s in most cases. Conclusion: Stealth liposomal doxorubicin has activity in refractory epithe lial ovarian cancer. PPE and stomatitis can usually be managed by dose adju stment, The ease of administration makes this an attractive agent. (C) 2000 by American Society of Clinical Oncology.