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Treatmen of Pancreatic Cancer

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After pancreatic cancer has been diagnosed, a multidisciplinary committee of specialists in radiology, nuclear medicine, pathological anatomy, radiotherapy, oncology, digestive surgery, liver surgery, the digestive system, anaesthesia and advanced practice pancreatic nursing staff (nurses with experience in the management of toxicities related to chemotherapy and/or radiotherapy) will evaluate the clinical situation of the individual patient and agree on the best therapeutic option.

The type of treatment is chosen based on the following factors:

Patient characteristics. Age, other diseases that complicate certain treatments, and functional status (ability to carry out the activities involved in daily living).
Location of the tumour. Head, body, tail.
Phase or stage of the disease.

Surgical treatment of pancreatic cancer

Surgical treatment will vary depending on the affected area:

Head of the pancreas. The surgery of choice is a cephalic duodenopancreatectomy. The head of the pancreas is removed along with the duodenum (the first section of the small intestine), and the distal bile duct, including the gallbladder. The stomach may be entirely preserved or, sometimes, it may be necessary to remove the most distal portion, including the pylorus. After it is removed, the pancreatic duct, the bile duct and the stomach are reattached to the intestine.
Body or tail of the pancreas. A distal pancreatectomy with splenectomy is performed. a distal pancreatectomy with splenectomy is performed. The body and tail of the pancreas are removed.
Large size or occupies more than one section of the pancreas. A total pancreatectomy (including the spleen) is performed.

Complications of pancreatic cancer surgery

Pancreatic surgery is usually very safe when performed by experienced surgeons. However, given the degree of difficulty involved, it is possible for complications related to the procedure to arise. Those related to the pancreas itself are associated with the artificial attachment of the pancreatic duct to the intestine, and the removal of part of the gland. Pancreatic fluid can leak into the abdomen, which may lead to the digestion and swelling of surrounding tissues, and may impair the gland's function.

Because the pancreas produces enzymes and hormones for digestion, malabsorption syndrome can occur when part of it is removed. This is the inability to absorb nutrients from the gastrointestinal tract. Digestion can be improved by taking oral pancreatic enzyme supplements.

The pancreas also produces insulin, which controls blood sugar levels. It may be necessary to start insulin therapy following pancreatic resection. If the entire pancreatic gland is removed (total pancreatectomy), pancreatic enzyme supplements and insulin must be taken for life.

Other common complications of pancreatic surgery include delayed gastric emptying, which delays the reintroduction of oral intake of food, leaking bile fluid, and intra-abdominal haemorrhage.

Treatment with chemotherapy and radiotherapy

Chemotherapy. Chemotherapy is the most common type of treatment for pancreatic cancer. Chemotherapy is generally administered intravenously, although in some cases it can be administered orally. Chemotherapy inhibits the growth of cells in the process of division, both tumour cells and healthy cells. This causes the symptoms associated with the treatment, known as adverse effects or side effects.

Chemotherapy can be given as a combination of two drugs (polychemotherapy) or one drug (monotherapy). The most commonly used drugs include gemcitabine, fluoropyrimidines (5-fluorouracil, capecitabine), irinotecan, pegylated irinotecan, oxaliplatin and nab-paclitaxel.

The number of cycles depends on the patient and the tumour stage, although generally speaking treatment usually lasts 3-6 months. Throughout the course of the treatment, different tests are carried out (analyses, imaging tests, etc.) to assess whether it is effective.

Radiotherapy. Radiotherapy administers high-energy X-rays to destroy cancer cells. It has different uses in pancreatic cancer and can be administered alone or in combination with chemotherapy to reduce the size of the tumour before surgery.

Treatment according to the stage of the disease

Resectable pancreatic cancer. Surgery is the only treatment that can cure pancreatic cancer. Adjuvant treatment with gemcitabine or modified Folfirinox is indicated in resected patients, resulting in increased 5-year survival rates.
Borderline resectable or locally advanced pancreatic cancer. In borderline resectable or locally advanced patients, i.e., those who have a high risk or impossibility of undergoing a complete surgical resection of the tumour, neoadjuvant treatment is recommended (usually based on chemotherapy or a combination of chemotherapy and radiotherapy that is administered prior to surgery, with the intention of creating better conditions for the surgery). Many patients with borderline disease and some with locally advanced disease respond to neoadjuvant treatment, and when it has been completed, they can undergo surgery with better chances of complete tumour resection, therefore improving their chances of curing the disease.
Stage IV pancreatic cancer. Standard treatment is FOLFIRINOX or gemcitabine/nab-paclitaxel, as they have demonstrated benefits over gemcitabine monotherapy and are indicated in patients with ECOG PS 0-1. In patients with ECOG PS 2, gemcitabine monotherapy is the treatment of choice. This patient population is under-represented in studies and is more susceptible to presenting toxicity. Second-line treatment options would be FOLFOX or Naliri (Onivyde).

Complications of chemotherapy treatment

Treatment has different side effects, depending on the specific type of chemotherapy administered.

Symptoms that may occur include: tiredness (asthenia), alterations in the sense of taste, nausea, vomiting, alopecia, inflammation of the oral mucosa, fever, constipation/diarrhoea, muscle pain, neurotoxicity (pain, tingling or loss of sensation in fingers/toes), redness, pain and wounds on hands/feet, acneiform rash and lesions on the nails.

Chemotherapy with gemcitabine/nab-paclitaxel can cause alopecia, diarrhoea, and haematological toxicity. It can also cause skin erythema and, on rare occasions, mouth sores (mucositis). If these side effects occur, it is important to discuss them with your regular doctor.

The combination of oxaliplatin with fluorouracil in continuous infusion (FOLFOX) can also cause mucositis and diarrhoea. The treatment usually also causes moderate tiredness, particularly during the first few days following treatment. Oxaliplatin may also cause neurotoxicity (numbness in the hands and feet), particularly after 8-12 cycles of treatment. This side effect may persist even once administration of the treatment has been stopped.

The other chemotherapy combination (FOLFINIROX) may cause diarrhoea, abdominal pain, and a greater degree of alopecia than FOLFOX, associated with neurotoxicity.

New therapies

Targeted therapy is the use of drugs directed towards a characteristic that is specific or unique to cancer cells, and that healthy cells do not have. Because these drugs specifically target cancer cells, they are less likely to damage normal cells in the rest of the body.

When it comes to new therapies in pancreatic cancer, it is important to know that it is a paradigmatic example of a low-grade tumour at the immunogenic level, due to the high presence of stroma and poor lymphocyte infiltration. PD1 and PD-L1 inhibitors have not been shown to be effective in pancreatic cancer. Combinations of PD1 or PD-L1 inhibitors associated with vaccines or combinations of PD1 or PD-L1 associated with drugs that deplete the stroma and the cytokines that they produce are strategies currently being assessed.

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