Caelyx®: phase II studies in ovarian cancer

Abstract

While there have been significant advances in first-line chemotherapy for advanced ovarian cancer, most patients still relapse with drug-resistant disease. For patients refractory to the two most active agents (platinum and paclitaxel), there are few salvage regimens that possess significant clinical activity together with minimal treatment-related toxicities. Caelyx® is a new treatment for advanced ovarian cancer, which delivers doxorubicin encapsulated in long-circulating Stealth® liposomes, resulting in a prolonged circulation and enhanced tumour targeting of the drug, together with a markedly different safety profile compared with native doxorubicin. Recent phase II clinical trials in relapsed ovarian cancer have demonstrated efficacy in patients with platinum-refractory disease (defined as progression on or relapse within 6 months of previous therapy). In those with combined platinum/paclitaxel-refractory disease, the response rate was 14.5% (95% Confidence Interval (CI): 7.8–21.4%), with many patients demonstrating a prolonged duration of response of beyond 6 months. The most frequent severe (grade 3/4) toxicity with Caelyx® was palmar-plantar erythrodysesthesia (PPE), which occurred in 25% of patients and was managed by dose modification or lengthening the treatment cycle. The incidence of neutropenia and alopecia was much reduced, and the cardiac safety profile was also improved compared with equivalent cumulative anthracycline doses for native doxorubicin. In summary, the evidence of clinical efficacy in patients with platinum-refractory ovarian cancer together with an improved safety profile are all strongly supportive of a positive benefit-risk profile for Caelyx® in the treatment of advanced ovarian cancer following failure of first-line platinum-based therapy