Survival benefit of adding Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) at the different time-points of treatment of ovarian cancer: review of evidence.

The standard treatment for advanced ovarian cancer consists in complete cytoreductive surgery (CRS) and intravenous combination chemotherapy with a platinum compound and a taxane. Although response rates to initial therapy are high, many patients will recur and die of peritoneal carcinomatosis. The addition of Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) to the standard therapy aims at increasing survival by reducing peritoneal recurrence. This review describes the survival results of HIPEC at the different time-points of the treatment of ovarian cancer: at upfront CRS, at interval CRS, at consolidation CRS after complete response to initial therapy, at secondary CRS after incomplete response, at salvage CRS for recurrence and as palliative treatment without CRS for unresectable ovarian cancer with chemotherapy resistant ascites. The available evidence suggests that a potential survival benefit of adding HIPEC may be largest in the settings of secondary CRS for stage III ovarian cancer and salvage CRS for recurrent ovarian cancer, two time-points representing failure of initial standard therapy. There is much less evidence for a potential benefit of HIPEC for less advanced stages (I-II) and for earlier time-points in the treatment of ovarian cancer (upfront, interval and consolidation). Postoperative mortality is not higher after CRS and HIPEC (0.7%) than after CRS only (1.4%). Four randomised trials are ongoing and their results are eagerly awaited. Palliative HIPEC without CRS might be used more in patients with incapacitating ascites due to recurrent ovarian cancer which has become resistant to systemic chemotherapy.

Long-term benefit of high-dose epirubicin in adjuvant chemotherapy for node-positive breast cancer: 15-year efficacy results of the Belgian multicentre study.

PURPOSE: The 4-year results of this trial demonstrated that a higher dose of epirubicin with cyclophosphamide (HEC) is superior to a lower dose of epirubicin, 60 mg/m(2) (EC), for event-free survival (EFS; 27% reduction), but is not superior to classical oral cyclophosphamide, methotrexate, and fluorouracil (CMF) in the adjuvant treatment of node-positive breast cancer. Herein we report the 15-year data on efficacy and long-term toxicity of this three-arm Belgian multicenter trial. PATIENTS AND METHODS: Between March 1988 and December 1996, 777 eligible patients were randomly assigned to six cycles of CMF, eight cycles of EC, or eight cycles HEC. RESULTS: The 15-year EFS was 45% for patients who received CMF, 39% for patients who received EC, and 50% for patients who received HEC. The hazard ratios (HR) were 0.77 for HEC versus EC (95% CI, 0.60 to 0.98; P = .03), 0.90 for HEC versus CMF (P = .39), and 0.86 for EC versus CMF (P = .21). No difference in overall survival (OS) was seen. Cardiac toxicity was more frequent with HEC than with CMF (11 patients v 1 patient; P = .006), but no more than with EC (P = .21). CONCLUSION: Treatment with HEC demonstrated superior EFS when compared with lower-dose epirubicin. However, we do not recommend the use of HEC regimen in daily clinical practice, mainly because of the higher risk of cardiotoxicity related to the cumulative doses of epirubicin and the lack of superiority of anthracyclines over CMF in our study.