OPINION STATEMENT:
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.
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