Treatment with palliative intent

Not all patients with peritoneal cancer can be treated with HIPEC. HIPEC may not be a viable option because the peritoneal cancer is too extensive, there are metastases outside the abdomen (e.g., metastases in the lungs) or the tumor of origin is not suitable for HIPEC (e.g., pancreatic cancer). Despite being diagnosed with such an aggressive disease, some patients are in a remarkably good clinical condition. These patients may be offered treatment with palliative intent, which strives to prolong survival and to resolve symptoms of the peritoneal cancer as much as possible and for as long as possible.

Additionally, when treatment is of a palliative nature, the treatment is usually a multidisciplinary effort, which may include the following aspects:

REMOVAL OF ASCITES Peritoneal cancer deposits may produce fluid that accumulates in the abdomen (“malignant ascites”). This fluid accumulation increases the size of the abdomen and may cause discomfort, difficulty walking or lying down, loss of appetite, difficulty eating or even shortness of breath. For severe complaints, removal of the ascites may be necessary. Ascites removal is usually accomplished by inserting a small catheter into the abdomen and connecting it to a drainage bag. This procedure is often performed in an outpatient clinic under local anesthesia and lasts a few hours before the catheter is removed. Unfortunately, the ascites may return and repeat drainage may be required. Sometimes, a permanent catheter can be inserted to facilitate repeat drainage.

SURGERY TO RESOLVE BOWEL OBSTRUCTION In some patients, a peritoneal cancer nodule obstructs part of the intestinal tract. This obstruction may be accompanied by abdominal cramps (“colic”). In some cases, the patient starts vomiting and is unable to eat and drink. To resolve the obstruction, surgery may be needed. Whenever possible, the obstructed segment of the intestinal tract is removed and the continuity of the gastrointestinal tract is restored. Sometimes, it is not possible to remove the cause of the obstruction. In such cases, healthy bowel located in front of and behind the obstruction is connected to “bypass” the obstruction and restore the abdominal tract. In advanced cases, no healthy bowel may be available to perform the bypass surgery. In these cases, an ileostomy or a colostomy may be required.

NUTRITION SUPPORT Patients suffering from peritoneal cancer may experience loss of appetite and abdominal pain that is made worse by eating. As a result, patients may develop malnutrition, which may be problematic for subsequent treatment. Advice from specialized nutritional support teams may help to prevent or diminish malnutrition. Specialized nutrition may be administered to the gastrointestinal tract itself (“enteral feeding”) or through the bloodstream (“parenteral feeding”).

PAIN RELIEF Patients in the advanced stage of colorectal cancer may experience acute and chronic pain. Expert advice and support for pain relief may restore physical functioning, increase activity levels and quality of life as well as decrease the psychological impact of pain on the patient.

Role of systemic therapy

Systemic chemotherapy consists of a group of medications designed to inhibit or destroy cancer cells. Such therapy may be administered through infusion, pills or a combination of both.

The success of chemotherapy depends on many factors including the origin of the peritoneal cancer. In women with peritoneal cancer with an ovarian origin, systemic therapy has proven to be very effective. In contrast, the role of systemic therapy in peritoneal cancer patients with a colorectal origin has been the subject of debate for a long time. “Old-fashioned” chemotherapy was not a very successful approach for these patients. This outcome gave peritoneal cancer a reputation as a “chemo-resistant” disease. However, better results are now obtained in colorectal cancer patients with combinations of modern chemotherapeutics and “targeted agents”.

Systemic chemotherapy: Depending on the origin of the peritoneal cancer, various chemotherapeutic drugs are currently available. For example, oxaliplatin, irinotecan and 5-FU are often prescribed either as single agent or in different combinations for peritoneal cancer with a colorectal origin. For ovarian cancer, cisplatin is frequently used.

Biologicals or “targeted agents”: Used in conjunction with “classical chemotherapy” as described above, these new drugs have recently become available for the treatment of patients with metastasized cancer. These drugs are referred to as “targeted agents” because they aim to specifically inhibit vital mechanisms within tumors. One such mechanism is the formation of new blood vessels needed to increase the blood supply of growing tumors, which is a process called “neo-angiogenesis”.

Observations in experimental laboratory studies suggest that peritoneal cancer nodules with a colorectal origin are capable of inducing neo-angiogenesis (see picture below).

Inhibiting neo-angiogenesis may thus be a promising strategy for the treatment of peritoneal cancer. Drugs that specifically inhibit this process, include bevacizumab, aflibercept and ramucirumab. These drugs have already been succesfully utilized for treatment of colorectal cancer with lung or liver metastases, mostly in combination with systemic chemotherapy. Small, but promising, non-randomised studies now also suggest that bevacizumab added to systemic chemotherapy may have a beneficial effect on patients with peritoneal cancer of colorectal origin (read paper). However, more research is required to define the exact role of systemic chemotherapy and targeted agents in the treatment of peritoneal cancer patients.

Overall, systemic therapy may have an important role in the treatment of select peritoneal cancer patients by relieving symptoms and prolonging survival. However, not all patients will benefit from systemic therapy. Side effects are common and may be severe.

Prior to treatment, most medical oncologists judge the clinical condition of a patient by determining “the performance status”. This approach is a relatively easy way to predict whether a patient may tolerate systemic therapy. The decision whether to treat a patient with systemic therapy should be considered by a multi-disciplinary team and based on many factors, including age, general condition, origin and severity of the peritoneal cancer.