Peritoneal Metastasis
Cancer originating from organs in the peritoneal cavity (e.g., ovarian, pancreatic, colorectal, gastric, liver and peritoneal mesothelioma) account for approximately 250,000 new cases of cancer annually in the USA.[10] Peritoneal metastases are common owing to the locoregional spread (e.g., incidences of 90, 50 and 32% in ovarian, pancreatic and colon cancer, respectively). In the peritoneal cavity, movement of cells tends to follow the circulation of peritoneal fluid from the right pericolic gutter cephalad to the right hemidiaphragm. Peritoneal metastasis can also be formed due to distant metastases of extraperitoneal cancers (e.g., pleural mesothelioma, breast and lung). Lodging of tumor cells in diaphragmatic or abdominal lymphatic ducts causes obstruction of lymphatic drainage and decreased outflow of peritoneal fluid, leading to formation of carcinomatosis or ascites.[11,12] Patients with carcinomatosis suffer from abdominal distention, loss of appetite, shortness of breath, abdominal pain, low blood pressure, weakness, fatigue and intestinal obstruction due to adhesions formed between intestinal loops.[13] The current treatment objectives for these patients are primarily palliative (e.g., pain control and repeated drainage of peritoneal fluid), and there are no meaningful therapeutic options.
Metastasis of an ovarian cancer can occur before its capsule is ruptured. Exfoliation and spreading of tumor cells can be IP and transperitoneal, and tend to follow the circulatory path of the peritoneal fluid.[14–16] Spreading through the lymphatics also occurs. In patients with advanced disease, peritoneal metastases are found in approximately 70% of cases and lymphatic dissemination to the pelvic and para-aortic lymph nodes in approximately 40% cases.[17] The most common extra-abdominal site of metastasis is the pleural space.[15,18]
Peritoneal metastasis of gastric and colorectal cancer involves infiltration of the serosal layer and peritoneal implantation.[19,20] Approximately 50% of patients with serosa-invasive gastric carcinoma develop peritoneal recurrence and die of this disease during the first 2 years. In colon cancer, peritoneal metastases are also frequent in patients with recurrent disease (~40% cases).
A part of the pancreas (tail) is located in the IP space. For the remaining parts of the pancreas (head, body and neck) that are located in the retroperitoneal space, there are multiple structures (e.g., reflections and ligaments) that enable transport and metastasis between the retroperitoneal space and IP space.[21–23] Approximately 20–30% of advanced pancreatic cancer is stage III locally advanced disease, where tumors have invaded nearby organs, such as the stomach, spleen, large bowel and nearby large blood vessels or major nerves. At the later stage (stage IV), tumors invade the peritoneum and form transperitoneal metastases.[24] Peritoneal metastases are common and found in approximately 70–80% of nonresectable patients. For example, autopsy of 974 pancreatic cancer patients has established that approximately 50% of patients had peritoneal metastases at time of death, and another 20–30% patients who otherwise did not have liver or peritoneal metastases showed malignant cells in the peritoneal cavity.[13]
Since patients with peritoneal metastases often also have distant metastases in systemic organs, intravenous therapy is usually the standard of care. Multiple clinical studies have shown that adding IP therapy to intravenous therapy provides additional disease control and prolongs patient survival in ovarian cancer patients with small tumors (<1 cm diameter). However, IP therapy does not appear to produce benefits in patients with larger tumors or carcinomatosis. As discussed in later sections, the lack of efficacy of IP therapy in these situations may be owing to the off-label use of intravenous drug formulations that have suboptimal PK/PD properties.
Future Oncol. 2010;6(10):1625-1641. © 2010 Future Medicine Ltd.
Cite this: Intraperitoneal Therapy for Peritoneal Cancer - Medscape - Oct 01, 2010.
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