Journal Club - December 2004

Long-term survival advantage for women treated with pegylated liposomal doxorubicin compared with topotecan in a phase 3 randomized study of recurrent and refractory epithelial ovarian cancer.
Gordon AN, Tonda M, Sun S, Rackoff W.
Gynecol Oncol. 2004 Oct; 95 (1):1-8. [Abstract]

Summary
Gordon and coworkers, writing for the Doxil Study 30-49 investigators, reported mature survival results of a prospective phase 3 study of patients with epithelial ovarian cancer that recurred after or failed to respond to first-line platinum-based chemotherapy randomized to receive either pegylated doxorubicin (Doxil) 50mg/m2 every 28 days or topotecan (Hycamptin) 1.5mg/m2 per day for 5 days every 21 days. Patients were stratified prospectively according to their initial response to platinum-based therapy (46% of patients had platinum-sensitive disease) as well as the presence or absence of bulky disease. The mature survival data were collected after 87% of patients had died, with 13% of patients censored from further observation. Overall, there was an 18% reduction in the risk of death for patients treated with pegylated liposomal doxorubicin (median survival 62.7 weeks for pegylated liposomal doxorubicin and 59.7 weeks for topotecan-treated patients; HR = 1.216; 95% confidence interval (CI) 1.000-1.478; P =0.050). The hazard ratio for all randomized subjects (includes those randomized, but never treated; n = 481) was 1.23 (median survival 63.6 weeks for pegylated liposomal doxorubicin and 57.0 weeks for topotecan-treated patients; 95% CI 1.01-1.50; P = 0.038). For patients with platinum-sensitive disease, there was a 30% reduction in the risk of death for the pegylated liposomal doxorubicin-treated group (median survival 107.9 weeks for pegylated liposomal doxorubicin and 70.1 weeks for topotecan-treated patients; HR = 1.432; 95% CI 1.066-1.923; P = 0.017). In patients with platinum-refractory disease, survival was similar between treatment groups.

Discussion
The most effective chemotherapy regimen for recurrent or refractory ovarian cancer continues to be debated. This was a well-executed prospective study that confirms previously reported preliminary results indicating a modest advantage in long-term survival for patients treated with pegylated doxorubicin compared to topotecan. As with any treatment for recurrent ovarian cancer, the specific side effect profile of a proposed therapy must be considered in all treatment decisions.

Conclusion
Long-term follow-up demonstrates that treatment with pegylated liposomal doxorubicin significantly prolongs survival compared with topotecan in patients with recurrent and refractory epithelial ovarian cancer. The survival advantage was most pronounced in patients who had previously responded to platinum-based therapy followed by a disease-free interval of at least 6 months.

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