Dose-Dense Approaches to Ovarian Cancer Treatment

Currently, paclitaxel and carboplatin are administered every 3 weeks as the standard agents for the first-line treatment of advanced ovarian cancer. The concept of “dose-dense therapy” is based on the Norton-Simon hypothesis that a shorter interval between the doses of cytotoxic agents is more effective in reducing tumor burden than dose escalation. The results of phase III clinical trials demonstrating the superiority of weekly paclitaxel administration, compared with a 3-week schedule in breast cancer in both the metastatic and adjuvant settings support the hypothesis. The Japanese Gynecologic Oncology Group reported the results from a phase III study comparing the conventional paclitaxel and carboplatin every 3-week administration vs dose-dense weekly administration of paclitaxel combined with the every 3-week administration of carboplatin in advanced epithelial ovarian cancer, Fallopian tube, or primary peritoneal cancer. The median progression-free survival (PFS), the primary endpoint of this study, was substantially improved in the dose-dense treatment group (28 vs 17.2 months, hazard ratio [HR]: 0.71, 95 % CI: 0.58–0.88, P = 0.0015), and the overall survival (OS) at 3 years was also higher in the dose-dense treatment group (72 · 1 %) than in the conventional treatment group (65.1 %; HR 0.75, 0.57–0.98; P = 0 · 03). The long-term outcomes at a median follow-up period of 76.8 months were reported. The median PFS was significantly longer in the dose-dense regimen than in the conventional regimen (28.2 vs 17.5 months; hazard ratio [HR], 0.76; 95 % CI, 0.62–0.91; P = 0.0037), and the median OS was 100.5 months (95 % CI 65.2-∞) in the dose-dense regimen and 62.2 months (52.1–82.6) in the conventional regimen (HR, 0.79; 95 % CI, 0.63–0.99; P = 0.039; log-rank test). Dose-dense treatment offers a potential new standard of care for first-line chemotherapy for patients with advanced epithelial ovarian cancer. Ongoing studies will clarify the best dose, schedule, and route of administration.