Intraperitoneal Chemotherapy for Unresectable Peritoneal Surface Malignancies

Abstract

Malignancies of the peritoneal cavity are associated with a dismal prognosis. Systemic chemotherapy is the gold standard for patients with unresectable peritoneal disease, but its intraperitoneal effect is hampered by the peritoneal-plasma barrier. Intraperitoneal chemotherapy, which is administered repeatedly into the peritoneal cavity through a peritoneal implanted port, could provide a novel treatment modality for this patient population. This review provides a systematic overview of intraperitoneal used drugs, the performed clinical studies so far, and the complications of the peritoneal implemental ports. Several anticancer drugs have been studied for intraperitoneal application, with the taxanes paclitaxel and docetaxel as the most commonly used drug. Repeated intraperitoneal chemotherapy, mostly in combination with systemic chemotherapy, has shown promising results in Phase I and Phase II studies for several tumor types, such as gastric cancer, ovarian cancer, colorectal cancer, and pancreatic cancer. Two Phase III studies for intraperitoneal chemotherapy in gastric cancer have been performed so far, but the results regarding the superiority over standard systemic chemotherapy alone, are contradictory. Pressurized intraperitoneal administration, known as PIPAC, is an alternative way of administering intraperitoneal chemotherapy, and the first prospective studies have shown a tolerable safety profile. Although intraperitoneal chemotherapy might be a standard treatment option for patients with unresectable peritoneal disease, more Phase II and Phase III studies focusing on tolerability profiles, survival rates, and quality of life are warranted in order to establish optimal treatment schedules and to establish a potential role for intraperitoneal chemotherapy in the approach to unresectable peritoneal disease. Supplementary Information The online version contains supplementary material available at 10.1007/s40265-022-01828-7.

Progress in the Treatment of Peritoneal Metastatic Cancer and the Application of Therapeutic Nanoagents

“…(3) The presence of the peritoneal−plasma barrier also prolongs the exposure time of cancer cells to chemotherapeutic drugs and reduces the systemic toxicity of chemotherapeutic drugs. 6,61,67 It is these advantages that have led to promising results for intraperitoneal chemotherapy in many clinical trials for the treatment of peritoneal metastatic cancer; for example, in a preliminary study in 2004, Mahteme et al showed that the addition of intraperitoneal chemotherapy to the treatment of peritoneal metastatic cancer resulted in a survival benefit for patients. 68 The selection of chemotherapeutic drugs is particularly important when intraperitoneal chemotherapy is used in clinical practice, which is also an important factor to ensure the good therapeutic effect of intraperitoneal chemotherapy in the treatment of peritoneal metastatic cancer.…”

“…(2) Intraperitoneal chemotherapy allows for higher intraperitoneal drug concentrations compared to intravenous administration, probably due to the peritoneal–plasma barrier, which limits the reabsorption of intraperitoneal chemotherapeutic drugs into the body circulation. (3) The presence of the peritoneal–plasma barrier also prolongs the exposure time of cancer cells to chemotherapeutic drugs and reduces the systemic toxicity of chemotherapeutic drugs. ,, It is these advantages that have led to promising results for intraperitoneal chemotherapy in many clinical trials for the treatment of peritoneal metastatic cancer; for example, in a preliminary study in 2004, Mahteme et al showed that the addition of intraperitoneal chemotherapy to the treatment of peritoneal metastatic cancer resulted in a survival benefit for patients …”

Nanoparticles for efficient drug delivery and drug resistance in glioma: New perspectives

“…Chemotherapy resistance is a common challenge in tumor therapy because tumor cells acquire resistance to chemotherapeutic drugs and are unable to effectively kill tumor cells 16,17 . This phenomenon is usually caused by biochemical mechanisms within the tumor cells, such as drug efflux, drug catabolism, DNA repair 18–23 .…”

Intraperitoneal chemotherapy for peritoneal metastases of gastric origin: a systematic review and meta-analysis

“…In patients with more extensive peritoneal metastases, repeated administration of cytotoxic drugs into the peritoneal cavity has been investigated. Normothermic catheter-based intraperitoneal chemotherapy and normothermic pressurized intraperitoneal aerosol chemotherapy (PIPAC) are methods to deliver intraperitoneal chemotherapy with a palliative intent 9 . In this way, higher intraperitoneal concentrations of cytotoxic drugs can be achieved compared to intravenous administration 9 .…”

“…Normothermic catheter-based intraperitoneal chemotherapy and normothermic pressurized intraperitoneal aerosol chemotherapy (PIPAC) are methods to deliver intraperitoneal chemotherapy with a palliative intent 9 . In this way, higher intraperitoneal concentrations of cytotoxic drugs can be achieved compared to intravenous administration 9 . For normothermic catheter-based intraperitoneal chemotherapy, an access port is placed subcutaneously and connected to an intraperitoneal catheter.…”