Based on these randomized trials, the intraperitoneal route of administration for cisplatin and paclitaxel chemotherapy in the primary treatment of optimally resected stage III ovarian cancer is an acceptable therapeutic alternative to intravenous chemotherapy with carboplatin and paclitaxel (216). There are no reports of randomized direct comparisons of this intraperitoneal regimen to intravenous carboplatin and paclitaxel or to intraperitoneal carboplatin and paclitaxel. Intraperitoneal therapy can be used in patients with optimally resected tumors who have a good performance status and are in overall good health. Because intraperitoneal chemotherapy is more cumbersome and has a higher morbidity than intravenous therapy, the use of this technique of drug delivery should be individualized after thorough discussion with the patient.
The Japanese GOG randomized 637 patients with ovarian cancer to receive carboplatin AUC 6 and paclitaxel 180 mg/m2 every 3 weeks or the same dose of carboplatin and 80 mg/m2 paclitaxel every week for at least six cycles (217). The median progression-free survival was 28 months in the dose-dense arm and 17 months in the control group, and they reported relatively little difference in toxicity between the two arms and that grade 3 to 4 neurotoxicity in particular was very low. In the 417 patients who had stage III disease, about half had less than 1 cm maximum residual disease, similar to the patients in GOG 172. There is no subgroup analysis to determine whether these optimally debulked patients fared better with dose-dense paclitaxel, but the hazard ratio for recurrence was 0.69 for stage III as a group. These findings are very encouraging but need to be validated in another study. There is good evidence that weekly paclitaxel is more effective than paclitaxel every 3 weeks in breast cancer and the Japanese GOG study suggests that the same may apply to ovarian cancer. This important question is being studied in GOG and other studies comparing intravenous dose-dense treatment with intraperitoneal chemotherapy.
Some authors suggested that selected patients with suboptimal stage III and stage IV disease and those with large volume ascites and pleural effusions should have chemotherapy prior to debulking surgery. A series performed by Schwartz et al. suggested that these patients treated with neoadjuvant or cytoreductive chemotherapy had survival that was comparable to those patients treated in the same institution with debulking surgery followed by conventional chemotherapy (218). It is accepted that two or three cycles of chemotherapy before cytoreductive surgery may be helpful in patients with massive ascites and large pleural effusions. The chemotherapy may “dry up” the effusions, improve the patient’s performance status, and decrease postoperative morbidity, particularly chest morbidity (219,220).
The EORTC completed a large randomized trial in 718 patients with advanced ovarian cancer comparing initial surgery followed by six cycles of carboplatin and paclitaxel with three cycles of neoadjuvant chemotherapy followed by surgical debulking and another three cycles of chemotherapy. The study found that the progression-free survival was identical in both arms (12 months) and similarly the overall survival (30 months) was the same in both arms (221). The morbidity of surgery was significantly less in patients receiving neoadjuvant chemotherapy, suggesting that in selected patients with very advanced (stages IIIC and IV) ovarian cancer two to three cycles of neoadjuvant chemotherapy prior to surgical debulking is a reasonable option.