Ovarian Epithelial Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI] - Stage III and Stage IV Ovarian Epithelial Cancer Treatment
Since the adoption of the platinum-plus-taxane combination as the standard nearly worldwide, clinical trials have demonstrated:
- Noninferiority for carboplatin plus paclitaxel versus cisplatin plus paclitaxel.[18,19,20]
- Noninferiority for carboplatin plus paclitaxel versus carboplatin plus docetaxel.
- No advantage but increased toxic effects by adding epirubicin to the carboplatin plus paclitaxel doublet.
- Noninferiority for carboplatin plus paclitaxel versus sequential carboplatin-containing doublets with either gemcitabine or topotecan; or, triplets with the addition of gemcitabine or pegylated liposomal doxorubicin to the reference doublet as shown below:[23,24]
- From February 2001 to September 2004, the Gynecologic Cancer InterGroup trial GOG-0182 randomly assigned 4,312 women with stage III or stage IV epithelial ovarian or primary peritoneal cancer to four different experimental arms and to a reference treatment consisting of carboplatin (AUC 6) and paclitaxel (175 mg/m2) every 3 weeks for eight cycles. Stratification factors were residual-disease status and the intention to perform interval debulking surgery. Lethal events attributable to treatment occurred in less than 1% of patients without clustering to any one regimen. None of the experimental regimens were inferior. With a median duration of follow-up of 3.7 years, the adjusted relative risk of death ranged from 0.952 to 1.114, with the control arm achieving a PFS of 16.0 months and a median OS of 44.1 months.
In this large study consisting of 84% to 87% of patients with the Féderation Internationale de Gynécologie et d'Obstétrique stage III disease, as expected, the extent of cytoreduction was an important prognostic factor in OS. Results of PFS in patients with residuum greater than 1cm, less than or equal to 1 cm, or microscopic were 13, 16, and 29 months, respectively; whereas for OS, the results were 33, 40, and 68 months, respectively.
A trial of the Japanese Gynecologic Oncology Group (JGOG-3601 [NCT00226915]) circumvented this treatment trend and included patients with stage II through stage IV disease in addition to the patients undergoing neoadjuvant therapy. With results initially published in 2009 and long-term results updated in 2013, the JGOG-3601 has stimulated a number of other trials that address weekly dosing schedules versus the conventional every-3-weeks (intermittent) dosing in first-line epithelial ovarian cancer.[25,26,27] Conducted between 2003 and 2006, the Japanese trial accrued 637 patients and randomly assigned them to a range of six to nine cycles of the weekly (named "dose-dense") 80 mg/m2 of paclitaxel or to the usual intermittent schedule of paclitaxel at 180 mg/m2. Both regimens were given with carboplatin (area under the curve 6) in every-3-weeks cycles. With a primary endpoint of progression-free survival (PFS), an increase from 16 to 21 months in the PFS of the weekly paclitaxel-based regimen was sought.