As ovarian cancer spreads over the surface of the peritoneum and often recurs at this site, investigators have evaluated intraperitoneal (IP) administration of chemotherapy that can achieve high local concentrations of drug. A randomized, prospective trial performed by the Southwest Oncology Group (SWOG) and the GOG compared IP cisplatin (100 mg/M₂) to IV cisplatin (100 mg/M₂), each given with II cyclophosphamide (600mg/M₂), in patients with disease less than 2 cm in diameter. The intraperitoneal cisplatin arm had a significantly longer overall median survival than the intravenous arm, 49 versus 41 months (p = .03). In the patients with the least residual disease (< 0.5 cm maximum residual), however, there was not a statistically significant difference in median survival between the two treatments, 51 versus 46 months (p = .08).

Results of this randomized trial became available as paclitaxel was being incorporated into clinical practice. In a follow-up trial conducted by the GOG, a standard regimen of IV cisplatin (75 mg/M₂) and IV paclitaxel (135 mg/M over 24 h) was compared to a dose-intense regimen that was initiated by giving moderately high-dose carboplatin (AUC=9) for two induction cycles followed by IP cisplatin 100 mg/M₂ and IV paclitaxel (135 mg/M₂ over 24 h). The dose-intense arm produced slightly better progression-free median survival (27.6 months vs 22.5 months, p = .02), but there was not a statistically significant difference in overall survival (52.9 months vs 47.6 months, p = .056).

A randomized prospective GOG study is comparing IP cisplatin and paclitaxel to IP cisplatin and paclitaxel. Based on results of currently available studies, the value of intraperitoneal chemotherapy in the primary treatment of optimally resected stage III ovarian cancer remains unclear.

Neoadjuvant Cemotherapy
Some authors have suggested that, for patients with suboptimal stage III and stage IV disease, chemotherapy may be given in lieu of cytoreductive surgery. A series performed at Yale by Schwartz and colleagues suggested that the survival of patients treated with “neoadjuvant” or cytoreductive chemotherapy was comparable to those patients historically treated with cytoreductive surgery followed by conventional chemotherapy in the same institution. As other authors have shown a benefit to debulking patients prior to chemotherapy, the issue would need to be resolved by a prospective clinical trial. However, two or three cycles of chemotherapy prior to cytoreductive surgery may be helpful in patients with massive ascites or large pleural effusions. Chemotherapy may eliminate the effusions, improve the patient’s performance status, and decrease postoperative morbidity, particularly within the chest.

Radiotherapy in Advanced Invasive Disease
In the past decade, several studies have refined our knowledge of the possible benefits of radiation therapy in ovarian cancer. In particular, subgroups of patients have been identified who are most likely to have a curative benefit when radiation therapy is used as the sole postoperative treatment. In addition, the technical aspects of whole abdominal radiation (WAR) have been worked out, permitting therapy to be delivered with acceptable late toxicity (

Table 118-6). Despite this knowledge, WAR is not used widely.

Table 118-7 summarizes long term survival or relapse free rates from six published studies of whole abdominal radiation therapy for patients with advanced ovarian cancer. 271-276 The results of these studies are concordant in showing long-term failure-free survivors determined both by the stage at presentation and by the volume of residual disease, as expressed by the largest diameter of the largest remaining lesion. Between 38% and 62% of patients with identified residual disease less than 2 cm in diameter were cured after whole abdominal and pelvic irradiation. Most of the long term survivors had stage II disease, in which the postoperative tumor residuum was confined to the pelvis and was encompassed in the boost volume, where radiation doses are significantly higher than can be delivered to the upper abdomen. For patients with larger residual lesions, the probability of cure is small, in the neighborhood of 5% to 15%. These studies provide strong evidence that whole abdominal irradiation is therapeutic for patients with small-volume residual ovarian cancer, but questions have been raised about the interpretation of these results in the context of more modern surgical techniques and more effective chemotherapy. These studies were performed in an era when aggressive cytoreductive surgery and comprehensive surgical exploration of the abdominal contents were not uniformly performed.