Ovarien cancer

Epithelial ovarian cancer (EOC) is the fifth most frequent cancer among females and approximately two thirds of the patients present with advanced disease (International Federation of Gynecology and Obstetrics [FIGO] stage III or IV) at diagnosis . The current standard treatment for these patients consists in maximum cytoreductive surgery (CRS) and platinum-based chemotherapy . Although platinum drugs are the most active agents in ovarian cancer, taxanes have emerged as an important group of drugs, particularly when given in conjunction with platinum. Though the response rate for first line carboplatin and paclitaxel (PTX) is 70% to 80%, this approach still yields poor results and overall 5-year survival rate is less than 30%. Several studies have sought to improve survival by addition of a third agent (topotecan, gemcitabine, doxorubicin) without any survival advantage. Currently the 3rd International Gynecologic Cancer Intergroup Ovarian Cancer Consensus Conference (Baden-Baden, Germany, 2004) proposed carboplatin and PTX as standard of care and as the favored standard treatment protocol for comparison in clinical trials . In ovarian cancer, the peritoneal cavity is the main site of disease diffusion and the administration of chemotherapy into the peritoneal cavity increases the drug's dose delivered to the tumor site without compromising plasma drugs levels. Based on this idea, three studies compared intravenous versus intraperitoneal (IP) administration of cisplatin (CDDP) and PTX and showed an increase of median survival in the IP treatment group. Based on these results, the US National Cancer Institute prompted a clinical announcement in 2006 stating that IP chemotherapy should be considered for optimally debulked patients. Despite the advantage of this approach, IP chemotherapy has not become routine practice because of major toxicity, lack of experience in placing and managing indwelling catheters, and the difficulty to diffuse the drugs in all peritoneal cavity due to adhesions and anatomic niches. In recent years, maximum cytoreductive effort combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has been a promising treatment for non-ovarian carcinomatosis (e.g., carcinoma of the appendix, or colon). The procedure exploits the advantages of IP therapy and the synergistic enhancement of drug cytotoxicity induced by heat. Various protocols have been described using CDDP, doxorubicin, mitomycin C, oxaliplatin, interferon α, and mitoxantrone . These drugs have been chosen because of their favorable IP pharmacokinetics and their high local efficacy. Recently there are published phase III randomized  trials with significant advantage with adding  HIPEC after citoreduction.