Adding topotecan to carboplatin plus paclitaxel, the standard treatment for ovarian cancer, does not improve progression-free survival in patients and leads to greater toxicity, according to a study published online October 11 in the Journal of the National Cancer Institute.
Cisplatin plus paclitaxel, and carboplatin plus paclitaxel, are the most widely accepted first-line regimens for advanced epithelial ovarian cancer. Still, most women relapse and die from their disease. One possible solution is to add a third agent, such as topotecan, which has activity in the treatment of recurrent disease. However, combining topotecan with carboplatin plus paclitaxel as a triplet therapy is problematic because of bone marrow toxicity. So, to integrate topotecan into the standard regimen researchers tested cisplatin plus topotecan followed by carboplatin plus paclitaxel.
The phase III randomized study included 819 women aged 28-78 with newly-diagnosed stage IIB or more advanced ovarian cancer. The study was led by Paul Hoskins, M.D., of the British Columbia Cancer Agency in Vancouver and colleagues from three other groups: the NCIC Clinical Trials Group at Queen's University in Kingston, Canada, the European Organization for Research and Treatment of Cancer - Gynecologic Cancer Group, European Union, and the Grupo Espańol de Investigaci-n en C-ncer de Ovario in Spain.
The women in the study were from Canada and Europe, and were randomly assigned to one of two study groups: the first arm received cisplatin and topotecan, followed by carboplatin and paclitaxel; the second arm received only carboplatin and paclitaxel.
The researchers found that after a median follow-up of 43 months, 650 patients had disease progression and 406 had died. The progression-free survival of patients in the first arm was 14.6 months compared to 16.2 months for those in the second arm. Furthermore, although survival data were not mature, there is no evidence to date that patients receiving topotecan had improved survival (with a median overall survival of 42.3 months for patients in the first arm, compared to 42.1 months for those in the second).
Patients in the first arm also had more toxicity than those in the second. The common side effects included gastrointestinal symptoms, myelosuppression, neurological toxicity and myalgia. Patients in the first arm had more myelotoxicity, nausea and vomiting, while patients in the second had more neurosensory effects and allergic reactions.