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Advances continue to be made in tumor immunology and in strategies to integrate the growing number of bioimmunotherapeutic molecules into the treatment of ovarian cancer, as well as other malignancies. Extensive studies have provided support for antigen-driven T-cell activation in vivo. The number of known tumor antigen epitopes is expanding, although advances in this area remain behind that of melanoma. Evidence suggests that the tumor environment is contributing to a state of in vivo immunosuppression; however, in vitro experiments and laboratory correlative studies also show that immune suppressor activity might be reversible. These findings could lead to new approaches, such as the use of antibodies or cytokines to overcome the immunosuppressive effects, in addition to the more established surgical and chemotherapeutic debulking. Both prophylactic and therapeutic bioimmunotherapeutic strategies require pharmacodynamic and immunologic end points that can guide each phase in the development of an effective approach. Review of systemic and intraperitoneal (IP) immunotherapy trials of interferon (IFN) α, IFNγ, and interleukin 2 (IL2), as well as newer agents such as IL12 and Flt3 ligand, overall continues to offer promise of a role for bioimmunotherapy in the treatment of ovarian cancer. Future developments lie in the improved target specificity of activated cells and cell-surface-binding molecules and in a systematic plan for combining chemotherapy with cytokines, growth factors, and polyvalent vaccines that are based on the in vivo dynamics of each agent. Another totally different approach, which could set a new paradigm, might be to target cells from the inflammatory immune system, which could contribute to tumor growth, invasion, and metastasis. [ABSTRACT FROM AUTHOR]

Intraperitoneal (IP) chemotherapy for advanced ovarian cancer improves both overall and disease-free survival. In this chapter, we compare the effectiveness of intravenous (IV) to IP chemotherapy. The evidence suggests an improvement in survival if some of the chemotherapy is administered via the IP route. The adverse events principally relate to the presence of a peritoneal catheter, including pain, catheter blockage, gastrointestinal effects, and infection. A systematic search identified eight relevant randomized trials studying 1,819 women receiving primary treatment for ovarian cancer. Women were less likely to die if they received an IP component to the chemotherapy (hazard ratio = 0.80; 95% confidence interval [CI] = 0.71-0.90). Administering a component of chemotherapy by the IP route also prolongs the disease-free interval (0.79; 0.69-0.90) by almost 9 mo and increases complete response rates. There may, however, be greater pain, fever, and gastrointestinal toxicity, but less ototoxicity, using the IP route. [ABSTRACT FROM AUTHOR]

The mathematical modeling concepts developed by Robert Dedrick and his colleagues, and subsequent preclinical evaluation, provided a strong framework upon which to build a clinical investigative program examining intraperitoneal (IP) chemotherapy as a management approach in advanced ovarian cancer. These investigative efforts suggested the type of antineoplastic agents that should be explored, the patient populations more likely to benefit, and the limitations and potential toxicities of this novel strategy. [ABSTRACT FROM AUTHOR]

To date, the accomplishment in the area of regional treatment of ovarian cancer has been a major advance in the management of this difficult malignancy. What began as a hypothesis, based on a theoretical mathematical model, has been translated into a 67-mo median survival for women with small-volume residual advanced ovarian cancer (1). The three major randomized clinical trials on ovarian cancer are detailed in this chapter. The methodology and outcomes, as well as a critique of their design, are presented. Outcomes of these trials to date are described. [ABSTRACT FROM AUTHOR]

Although striking evidence exists that argues for the usefulness of hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal carcinomatosis (PC), many aspects of this therapy have yet to be standardized. As interest in this modality increases, there are several avenues of research to be explored. How important is the cytoreductive effort, the temperature elevation increment, and the length of time for the hyperthermic perfusion? We review what is known and what may be explored in the near future. [ABSTRACT FROM AUTHOR]

Hyperthermic intraperitoneal chemotherapy (HIPEC) was first delivered to a human in 1979 by Dr. John Spratt at the University of Louisville when he treated a male patient with pseudomyxoma peritonei (1). In collaboration with other researchers, he developed a delivery system using a "closed" technique, with both the fascia and skin closed. Since that time, there has been increasing interest around the world in the delivery of HIPEC. The most widely used methods have involved perioperative perfusion of chemotherapy in heated perfusate performed at the time of open laparotomy (see the following sections), but delivery of HIPEC has also been reported with laparoscopic placement of inflow and outflow tubing (2) and regional (3) and whole-body hyperthermia (4). Hyperthermic intraperitoneal chemotherapy requires an organized team within the operating room who all understand their roles. The anesthesiologist manages the cooling of the patient's core temperature before the hyperthermic perfusion and monitors the patient's vital parameters, particularly the core temperature, during the perfusion. The perfusionist, often recruited from cardiac surgery because of experience with the techniques of cardiopulmonary bypass, operates the heat exchange pump and equipment for the perfusion. Although it is everyone's responsibility, the scrub technicians and circulating nurses are charged with the specific duty of ensuring proper adherence to operating room protocol for the use of hazardous agents. The two main techniques for hyperthermic IP perfusion are "open," where the incision is open during the HIPEC, and "closed" where the abdominal skin and/or fascia are closed. Both basic methods have been extensively utilized, with many individual variations. In this chapter, the most widely used open technique, the "Coliseum," and the closed technique will be described and discusse [ABSTRACT FROM AUTHOR]

Research into the incorporation of hyperthermic intraperitoneal chemotherapy into treatment regimens for women with ovarian carcinoma has lagged behind that of other cancers causing peritoneal carcinomatosis despite the fact that ovarian cancer represents an excellent target for this modality of treatment. This chapter reviews experience with this technique from around the world, with the exception of France, and discusses future developments. [ABSTRACT FROM AUTHOR]

Epithelial ovarian cancers (EOC) represent 80%-90% of all ovarian malignancies, and they are the most common cause of death for all gynecological tumors in the Western world (1). The majority of patients have an advanced Federation of Gynecology and Obstetrics (FIGO) stage III or IV disease at presentation, but the disease is often confined to the peritoneal cavity (2). Current standard treatments of these patients consist of initial cytoreductive surgery (CRS) to <1-cm residual nodules, followed by combination systemic chemotherapy with a taxane and platinum analogue, either carboplatin or cisplatin. Our experience in France with a phase II prospective single-center study shows that the population is inhomogeneous, and >58% of patients underwent CRS and HIPEC after >2 prior recurrences and >2 laparotomies. Because of these multiple recurrences before inclusion, it was not possible to calculate the progression-free interval (PFI). In the literature, most of the series evaluating CRS alone are dedicated to secondary CRS, meaning that the patients are experiencing their first recurrence. The only feasible comparison between secondary CRS alone and this study could be on the completeness of cytoreduction, which appears as the most important prognostic factor. The present phase II study clearly underlines that combined salvage therapy can achieve long-term survival in some patients with second, third, or fourth locoregional recurrence from ovarian cancer. [ABSTRACT FROM AUTHOR]

Second to liver, the peritoneum is the most frequent site of metastases in colorectal cancer. In approximately 10% of patients, peritoneal carcinomatosis (PC) is already present at the time of initial diagnosis (1). PC is found in 30% of patients with recurrent colorectal cancer, either as part of more generalized metastases or as the only site. PC is the only site of tumor activity in 40% of cases (2). This means that approximately 8% of all colorectal cancer patients will have PC as their only site of cancer activity at some stage of their disease. PC is generally considered to represent distant metastasis and is staged as M1. Accordingly, until recently, treatment has been limited to palliative surgery, such as enterostomy or bypass to relieve obstruction, and systemic chemotherapy. There are few studies specifically reporting on the outcome of this approach in PC (3). Most studies on chemotherapy in metastatic colorectal cancer include all sites of metastases, with a dominance of liver metastases. Although some reports suggest that colorectal cancers recurring as PC are less likely to respond to systemic chemotherapy, there is little evidence for this. However, there is no doubt that PC patients have a shorter life expectancy than do patients with other metastatic sites, such as liver. This is probably explained by the difficulty in visualizing PC on scans, leading to relatively late diagnosis and the early development of bowel obstruction, even on relatively small tumor volumes. In our series at the Netherlands Cancer Institute, the diagnosis of PC in recurrent cases was made in 80% of patients during laparotomy for bowel obstruction. As a result, many patients will have either a (high output) ileostomy or a relative obstruction, making optimal chemotherapeutic treatment more difficult. In this circumstance, median survival is reported to be between 4 mo and 12 mo (4). [ABSTRACT FROM AUTHOR]

Cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC) has had a significant impact in the management of peritoneal surface malignancies of nongynecologic origin. It has improved the quality and quantity of life for these patients. Evidence of improved median survival has been observed independent of the origin of the carcinomatosis, and this treatment paradigm resulted in measurable 5-yr survival in diseases where it did not exist before the use of CRS + HIPEC. [ABSTRACT FROM AUTHOR]

Cancer ranks second only to heart disease as the greatest cause of mortality in the United States. Despite significant strides in diagnosis and therapeutics, clinical treatment of metastatic cancer still yields a poor prognosis. Basic science research is increasing our knowledge of the mechanisms by which chemotherapeutic and hyperthermic modalities exert their antitumor activity. Herein, we describe the current state of knowledge of these treatment modalities and the basic science behind their clinical usefulness. Moreover, we identify gaps in our understanding of the basic science of these treatments. Basic science is primed to exert a substantial role in extending our therapeutic options through the clarification of current therapeutic mechanisms, as well as the generation of novel treatments. [ABSTRACT FROM AUTHOR]

Ideally, the intraperitoneal chemotherapy (IP) delivery device is placed at the time of the original diagnostic procedure, when an optimal surgical resection can be completed. The patient, who is appropriately counseled before surgery about her risk of cancer and the treatment options available, should have an IP device placed at the time of surgical resection of the presumed ovarian or primary peritoneal cancer. The pathologic diagnosis and stage is not completely understood in that setting, but good clinical judgment can identify an appropriate candidate for IP chemotherapy. It is safer to place the device and remove it unused at the bedside later, than to forego placement and have to reoperate to place the device at a second procedure. The second procedure to place an IP catheter is an important barrier to initiating IP chemotherapy, and also delays proper treatment. [ABSTRACT FROM AUTHOR]