Treatment of Advanced Ovarian Cancer by Neoadjuvant Chemotherapy Followed by Surgical Debulking and Intraperitoneal Chemohyperthermia

Introduction: Ovarian cancer is particularly prone to peritoneal carcinomatosis (PC). Intraperitoneal chemohypertermia (HIPEC) has been proposed for treatment of PC from ovarian cancer with different results. Aim of the Study: This study was aimed at evaluating the effectiveness of HIPEC in primary ovarian cancer with PC. Methods: Between January 2000 and January 2009, HIPEC has been performed in 51 patients affected with advanced ovarian cancer; three patients were submitted to double treatment, for a total of 54 procedures. Forty-three patients were treated for primary ovarian cancer (group A), and 11 patients for tumor recurrence (group B). In group A, the stage of the disease was classifed as stage Ic in 1 case, IIa-IIc-IIIa in 2 cases respectively, IIIb in 1 case and IIIc in 35. After diagnosis and clinical staging, most of patients in group A were submitted to neoadjuvant chemotherapy with taxol and platinum schedule (6 cycles), and then they underwent surgery, according to a phase II protocol which is ongoing. Surgical treatment included hysteroannessectomy, appendectomy,removal of greater omentum and para-aortic lymphnodes, pelvic lymphadenectomy, and peritonectomy in abdominal regions with peritoneal metastases. After surgical debulking, HIPEC was carried out throughout the abdominopelvic cavity for 60 minutes, using a closed-abdomen technique. Intra-abdominal temperature ranged between 41°C and 43°C; mitomycin C (25 mg/mq) and cisplatin (100 mg/mq) were the anticancer drugs generally used, and they were administered with a flow rate of 700-800 ml/min. Results: Mean hospital stay was 11 ± 6 days (range 7-49). At the end of the operation, a complete cytoreduction (CCR-0) was obtained in 36 cases (67%); residual tumor < 2.5 mm (CCR-1) was observed in 8 cases (15%), and > 2.5 mm (CCR-2/3) in only 10 patients (18%). Postoperative complications occurred in 39% of cases. The most frequent complications were pleural effusion (6 cases), wound infection (5 cases), intestinal fistula (2 cases) and medical complications (5 cases). Grade-2 or more hematological toxicity occurred in 23 cases. Reoperation was necessary in two patients (4%). All complications solved favourably, and no perioperative or postoperative mortality was observed. With a mean follow-up period of 34 ± 21 months (range: 5-92), cumulative survival was 51% at five years; it was 54% in patients with primary tumor, whereas all patients with recurrent ovarian cancer died within 6 years from treatment. Long-term survival was also related to the absence of residual tumor (group A: 77% in CCR-0 vs. 16% in CCR+, p<0.005). Conclusions: Neoadjuvant chemotherapy followed by surgical treatment combined with HIPEC is an effective treatment for primary ovarian cancer with peritoneal dissemination; this approach is associated with a high rate of complete cytoreduction and long-term survival. Due to the high risk of postoperative complications, this treatment should be performed in specialized centers only.