Women given a more intensive 'dose-dense' regimen of chemotherapy survive longer and have a higher-rate of progression free survival, concludes an Article published Online First in an upcoming edition of The Lancet. The Article is written by Dr Noriyuki Katsumata, National Cancer Center Hospital, Tokyo, Japan, and colleagues.
Paclitaxel and carboplatin given every 3 weeks is currently considered standard first-line chemotherapy for advanced epithelial ovarian cancer. Paclitaxel and carboplatin have been combined with other drugs, given either concurrently or sequentially, in the hope of prolonging survival in women with advanced ovarian cancer, but the results of several randomised trials have been disappointing. Dose-dense weekly administration of paclitaxel is another strategy to enhance antitumour activity and prolong survival. In this study, the authors compared a conventional regimen of paclitaxel and carboplatin with a dose-dense weekly regimen in women with advanced ovarian cancer.
Patients with advanced epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer were eligible for this phase III randomised controlled trial at 85 centres in Japan. Patients given six cycles of either paclitaxel (180 mg/m²; 3-h intravenous infusion) plus carboplatin, given on day 1 of a 21-day cycle (conventional regimen; n=320), or dose-dense paclitaxel (80 mg/m²; 1-h intravenous infusion) given on days 1, 8, and 15, plus carboplatin given on day 1 of a 21-day cycle (dose-dense regimen; n=317). The primary endpoint was progression-free survival.
Median progression-free survival was longer in the dose-dense treatment group (28 months) than in the conventional treatment group (17 months). Overall survival at 3 years was also higher in the dose dense regimen group (72%) than in the conventional treatment group (65%). Expressed another way, women assigned to the dose-dense regimen had a 29% lower risk of disease progression and a 25% lower risk of death than those given the conventional regimen. 165 patients assigned to the dose-dense regimen and 117 assigned to the conventional regimen discontinued treatment early. Reasons for participant dropout were balanced between the groups, apart from withdrawal because of toxicity, which was higher in the dose-dense regimen group than in the conventional regimen group (n=113 vs n=69). Most patients in both groups experienced neutropenia (reduced white blood cell count). Severe anaemia was higher in the dose-dense treatment group (214 [69%]) than in the conventional treatment group (137 [44%]).
The authors say that the survival benefits shown in the dose-dense group are rare in women with advanced ovarian cancer. They conclude: "Dose-dense weekly paclitaxel plus carboplatin improved survival compared with the conventional regimen and represents a new treatment option in women with advanced epithelial ovarian cancer."
In an accompanying Comment, Dr Michael A Bookman, Arizona Cancer Center, Tucson, AZ, USA, says that confirmatory trials are now underway regarding dose-dense regimens. He concludes: "The use of such dose-dense therapy should be decided on an individual basis together with other options for women with advanced-stage ovarian cancer."
Dr Noriyuki Katsumata, National Cancer Center Hospital, Tokyo, Japan. T) +81-3-3542-2511ext.7027 E) nkatsuma@ncc.go.jp / nkatsumata@fiberbit.net
Dr Michael A Bookman, Arizona Cancer Center, Tucson, AZ, USA. E) mbookman@igcs.org
For full Article and Comment, see: http://press.thelancet.com/ovdosedense.pdf
Journal
The Lancet