In the ACTION trial, 440 patients from 40 European centers were randomized; 224 patients received adjuvant platinum-based chemotherapy, and 224 patients did not (188). Patients with As I and IIa, grades 2 and 3 were eligible. Only about one-third of the total group was optimally staged (151 patients). In the observation arm, optimal staging was associated with a better survival (HR = 2.31, p = 0.03), and in the suboptimally staged patients, adjuvant chemotherapy was associated with an improvement in survival (HR = 1.78, p = 0.009). In optimally staged patients, no benefit of adjuvant chemotherapy was seen. In the ACTION trial, the benefit from adjuvant chemotherapy was limited to the patients with suboptimal staging, suggesting that patients benefit only if they had a likelihood of occult microscopic dissemination.
When the data from the two trials were combined and analyzed, a total of 465 patients were randomized to receive platinum-based adjuvant chemotherapy and 460 to observation until disease progression (190). After a median follow-up of more than 4 years, the overall survival was 82% in the chemotherapy arm and 74% in the observation arm (HR = 0.67, p = 0.001).
Recurrence-free survival was better in the chemotherapy arm: 76% versus 65% (HR = 0.64, p = 0.001). The results of this analysis must be interpreted with caution, because most of the patients did not undergo thorough surgical staging, but the findings suggest that platinum-based chemotherapy should be given to patients who were not optimally staged.
Carboplatin is widely used instead of cisplatin, as it is equivalent in efficacy and much better tolerated with significantly fewer side effects (191). A randomized phase III trial of three versus six cycles of adjuvant carboplatin and paclitaxel in 457 patients with early stage epithelial ovarian carcinoma was conducted by the GOG (192). An unexpectedly large number of patients (126 patients, 29%) had incomplete or inadequately documented surgical staging in this study. The recurrence rate for six cycles was 24% lower (HR = 0.76; confidence interval [CI], 0.5– 1.13; p = 0.18) versus three cycles, but this was not statistically significant. The estimates of probability of recurrence at 5 years were 20.1% for six cycles and 25.4% for three cycles. The authors concluded that three cycles of adjuvant carboplatin and paclitaxel was a reasonable option for women with high-risk early stage ovarian cancer. The current GOG trial includes patients with high-risk stage I and stage II disease, and offers three cycles of carboplatin and paclitaxel followed by a randomization to either observation versus 26 weeks of weekly low-dose (40 mg/m2) paclitaxel. High-risk stage I is defined as stage IA or IB, grade 3, stage IC, or clear cell carcinomas.
The recommendations for therapy follow:
Patients with high-grade, high-risk stage I epithelial ovarian cancer should be given adjuvant chemotherapy. The type depends on the patient’s overall health and medical comorbidities
Treatment with carboplatin and paclitaxel chemotherapy for three to six cycles is used in these patients, whereas single agent carboplatin may be preferable for older women and patients with other medical comorbidities.