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 slower clearance rate than free doxorubicin, resulting in sustained serum levels. Liposomal encapsulation also leads to increased concentration of drug in tumor tissue. Meta-analysis of previous studies has shown that doxorubicin has activity in epithelial ovarian cancer. The current study was developed to examine the activity of Stealth liposomal doxorubicin in platinum- and paclitaxel-refractory ovarian cancer. Patients and Methods: Patients had epithelial ovarian cancer that either progressed on or recurred within 6 months of completion of platinum and paclitaxel chemotherapy. All patients had measurable disease. Stealth liposomal doxorubicin war administered at 50 mg/m(2) every 4 weeks as a 1 hour infusion. Results: Eighty-nine patients were treated and in eluded in an intent to-treat analysis. There were 82 patients who were platinum and paclitaxel refractory and met all study criteria, There was one complete response and 14 partial responses, for a total response rate of 16.9% (95% confidence interval [CI], 9.1% to 24.6%). For platinum- and paclitaxel-refractory patients, the response rate was 18.3% (95% CI, 9.9% to 26.7%), Median time to progression was 19.3 weeks for the entire population, Ten patients (11.2%) withdrew because of adverse events related to the drug (palmar-plantar erythrodysesthesia [PPE], n = 3; asthenia, n = 2; cardiac, n = 2; neutropenia, n = 1;stomatitis, 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. Stomatitis, PPE, and skin lesions were managed with dose reductions and delays in most cases. Conclusion: Stealth liposomal doxorubicin has activity in refractory epithelial ovarian cancer. PPE and stomatitis can usually be managed by dose adjustment, The ease of administration makes this an attractive agent. (C) 2000 by American Society of Clinical Oncology.