Dose-dense therapy is of benefit in primary treatment of ovarian cancer: contra.

Several studies in the past have tried to improve the prognosis of ovarian cancer by increasing the dose intensity of platinum. Only 2 out of 12 randomized studies showed survival benefit at the cost of significant long-term toxicity. Dose-dense induction therapy with combined weekly paclitaxel (at a dose of 90 mg/m(2)) and weekly carboplatin [at an area under the curve (AUC) of 4 mg·ml/min] followed by 3-weekly paclitaxel/carboplatin was very effective in platinum-resistant patients (response 58%, progression-free survival 10 months). In first-line, however, no survival benefit was found with the same dose-dense weekly paclitaxel/carboplatin regimen over standard-dosed 3-weekly paclitaxel/carboplatin in a randomized study. Very recently, the Japanese Gynecologic Oncology Group (JGOG) study no. 3016, randomizing patients in first-line between dose-dense weekly paclitaxel 80 mg/m(2) plus 3-weekly carboplatin AUC 6 and 3-weekly paclitaxel/carboplatin, showed a significant increase in progression-free survival (median 28 versus 17.2 months in the control arm; hazard ratio for progression, 0.71; 95% confidence interval, 0.58-0.88; P=0.0015). The 3-year overall survival was 72% versus 65% (P=0.03), respectively. The hematologic toxicity was substantial in both arms and substantially higher than observed with the weekly paclitaxel/carboplatin induction regimen. Many patients had treatment delays, dose reductions and stopped treatment prematurely. The JGOG 3016 study is the only dose-dense study with such a significant survival benefit. It is also the only dose-intensity study performed in Asian patients. Genotypes and phenotypes are thought to represent important determinants of drug efficacy in ovarian cancer. Therefore, confirmatory studies with this JGOG regimen together with translational research are needed in both Caucasian and Asian patients.