Principles and practice of intraperitoneal chemotherapy for ovarian cancer
Intraperitoneal (IP) chemotherapy has been studied for years to improve the survival of patients with ovarian cancer. Recently, the result of Gynecologic Oncology Group 172 trial comparing IP versus intravenous administration of cisplatin-based chemotherapy was published, demonstrating the improvement of survival benefit in favor of the IP arm. This trial is the third trial that showed a survival benefit on IP chemotherapy. The National Cancer Institute (NCI) and Gynecologic Oncology Group have done a meta-analysis on the results of these three US trials and other phase III trials of IP versus intravenous chemotherapy, and significant improvement of survival was shown with IP therapy. Based on this meta-analysis, NCI has released a clinical announcement encouraging the gynecological oncology community to consider IP chemotherapy as the standard treatment for optimally debulked advanced ovarian cancer patients. However, there still are controversial issues regarding the use of IP chemotherapy. It is important to understand how IP chemotherapy works to solve those issues in the future. In this review article, we discuss the principles and clinical aspects of IP chemotherapy and also discuss the current problems and future perspectives in IP chemotherapy.
Available from: Wim P Ceelen
- "In addition, different parameters must be considered to select the ideal chemotherapeutic agent for IP therapy and to maximize its efficacy: cavity-to-plasma AUC ratio, systemic absorption, depth of tumor penetration, and intrinsic activity of the agent against the primary tumor type. In general, water insoluble molecules with a high molecular weight and a high cavity-to-plasma AUC ratio remain longer in the peritoneal cavity and are thus preferred for IP treatment (Table 1) [23, 24]. One important consideration is that a high cavity-to-plasma AUC ratio does not automatically confer a higher efficacy, since penetration of the chemotherapeutic agent into the tumor might be limited. "
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ABSTRACT: Intraperitoneal (IP) chemotherapy is an effective way of treating peritoneal carcinomatosis of colorectal origin after complete cytoreduction. Although IP therapy has been already performed for many years, no standardized treatment design has been developed in terms of schedule, residence time, drug, or carrier solution. Because of the fast clearance of the conventional intravenous (IV) drug delivery systems used for IP therapy, a lot of research is performed to optimize IP drug delivery and extend the residence time of the cytotoxic agent in the peritoneal cavity. This paper reviews the recent advances made in drug delivery systems for IP chemotherapy, discussing the use of microparticles, nanoparticles, liposomes, micelles, implants, and injectable depots for IP delivery.
Available from: Pablo Ortega-Deballon
- "Despite recent improvements, the prognosis of patients with peritoneal carcinomatosis from digestive or ovarian origin treated with systemic chemotherapy remains poor [1,2]. Intraperitoneal chemotherapy (IPC) improves the control of regional disease in ovarian cancer and increases survival in carcinomatosis of colorectal origin [3,4]. Trials have shown a survival benefit with post-operative IPC versus intravenous administration of cisplatin-based chemotherapy in ovarian cancer [5,6]. "
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ABSTRACT: The best method to deliver intraperitoneal chemotherapy (IPC) for peritoneal carcinomatosis from ovarian cancer is not well defined. The aim of this study was to assess the ability of hyperthermia and adrenaline to enhance the intratumoral accumulation of cisplatin in a rat model of peritoneal carcinomatosis.
Four groups of 5 BDIX rats with ovarian peritoneal carcinomatosis underwent IPC with 30 mg/l of cisplatin according to the following conditions: normothermia at 37° for 1 or 2 hours, hyperthermia at 42°C for 1 hour or normothermia at 37°C for 2 hours with 2 mg/l adrenaline. Tissue platinum content was measured by atomic absorption spectroscopy. The effect of hyperthermia, adrenaline and the duration of exposure to the drug was measured in vivo (tissue concentration of platinum in tumor, abdominal and extra abdominal tissues) and in vitro (cytotoxicity on human ovarian cancer cells).
In vitro, hyperthermia and longer exposure enhanced the accumulation and the cytotoxic effect of cisplatin on cancer cells. In vivo, only the 2 hours treatment with adrenaline resulted in increased platinum concentrations. The rats treated with adrenaline showed significantly lower concentrations of cisplatin in extra peritoneal tissues than those treated with hyperthermia.
Adrenaline is more effective than hyperthermia in order to enhance the intratumoral concentration of cisplatin in rats with peritoneal carcinomatosis from ovarian origin. It may also decrease the systemic absorption of the drug.
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ABSTRACT: Trabectedin (Yondelis); ET-743) is an antineoplastic agent that was originally derived from the Caribbean marine tunicate Ecteinascidia turbinata and is now produced synthetically. It binds to the minor groove of DNA, disrupting the cell cycle and inhibiting cell proliferation. Intravenous trabectedin administered once every 3 weeks is approved as monotherapy in Europe for use in patients with advanced soft tissue sarcoma (STS) after failure of standard therapy with anthracyclines or ifosfamide, or who are unsuited to receive these agents. It also has orphan drug status in STS in the US and in ovarian cancer in the US and Europe, and is under investigation as combination therapy in patients with recurrent ovarian cancer. In clinical trials, trabectedin showed efficacy in the treatment of patients with advanced or metastatic STS, especially those with leiomyosarcoma or liposarcoma, as well as in women with platinum-sensitive advanced or recurrent ovarian cancer. In addition, its tolerability profile was generally manageable. The introduction of trabectedin expands the currently limited range of effective treatment options for patients with advanced or metastatic STS; trabectedin also has the potential to be a beneficial treatment for advanced or recurrent ovarian cancer.
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