Chemotherapy for pancreatic cancer

Chemotherapy describes the use of chemicals or drugs to fight cancer by destroying the cancer cells. There are many different drugs available which can be used in a variety of ways depending on the type of cancer, where it is located, how advanced it is and the general health and fitness of the patient.

How it works

Chemotherapy is used at various stages of of the cancer cell cycle. It can be used on its own or alongside other treatments such as radiotherapy or surgery. It works by killing cancer cells that are dividing to make two cells. Cancer cells divide much more frequently and in an uncontrolled manner compared to normal healthy cells, so the chemotherapy drugs will have a bigger effect on the abnormal cancer cells.

However because the drugs work by damaging dividing cells, it means that some normal cells will also be affected. These are those parts of the body where cells are being constantly replaced - such as hair, skin, bone marrow and blood, and the lining of the digestive system. This means there are usually side-effects such as sickness, diarrhoea, loss of hair, and susceptibility to infections. Usually the side-effects disappear when the treatment is over.

Not everyone will respond to chemotherapy treatment in the same way, and every patient is monitored during the course of therapy. Some chemotherapy drugs are given by injection into a vein, and others may be given as a tablet.

When chemotherapy is used for pancreatic cancer

Chemotherapy drugs can be used in a number of ways in the treatment of pancreatic cancer;

  • Following surgery
  • In advanced disease
  • In combination with radiotherapy
  • Before surgery

Following surgery

If your cancer has been totally removed you may be offered chemotherapy after surgery. This is to try to reduce the chances of the cancer coming back and is called adjuvant chemotherapy.

A trial called ESPAC-1 showed that chemotherapy with 5FU/FA (5- fluorouracil/ folinic acid) after surgery can reduce the risk of the cancer coming back.

The follow-up trial to ESPAC-1 was called ESPAC-3 (v2). This trial compared 5FU/FA with gemcitabine (GEM) after surgery to see which drug is better at reducing the chances of the cancer coming back. This was the largest adjuvant trial ever conducted for pancreatic ductal adenocarcinoma (over 1,000 patients recruited from 16 countries) and showed no significant difference in survival between adjuvant 5FU/FA and adjuvant GEM.

Currently the ESPAC 4 trial is comparing the standard therapy of gemcitabine to a combination of gemcitabine given with a chemotherapy tablet called capecitabine (GemCap). Patients are still being recruited for this trial which is due to close in September 2014.

In advanced disease

If your cancer has spread beyond the pancreas, chemotherapy can be used to relieve your symptoms and to try and shrink the disease. The chemotherapy will not cure the cancer but may help slow its growth for a period of time.

The drug used most commonly in this instance in the UK is gemcitabine. An important trial undertaken in the 1990s demonstrated the benefit of gemcitabine chemotherapy in improving both symptom and disease control. Gemcitabine has NICE approval for use in the UK for locally advanced and metastatic pancreatic cancer.

In recent years many trials have examined new treatments designed to improve on the results achieved with gemcitabine. The GemCap combination treatment is also being used for some patients with advanced disease by some centres in the UK, and is being used as the basis for future UK trials. See our page on clinical trials for pancreatic cancer for more information.

In May 2011 the results of a French study found that a chemotherapy regimen consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) showed an increased survival benefit in patients with metastatic pancreatic cancer compared to gemcitabine treatment. However this combination also lead to increased side effects. This treatment regimen may provide a new treatment option for patients with metastatic cancer who are relatively well.

Other drug combinations have been studied such as the combination of erlotinib (Tarceva) and gemcitabine. Ongoing trials are taking place to test the impact of various combinations of gemcitabine, erlotinib and capecitabine together with other agents such as bevacizumab or vaccine therapies.

Other trials have investigated the use of gemcitabine with platinum drugs (cisplatin and oxaliplatin) and some specialists use this drug combination.

It appears that drugs are more effective in some patients than others and it has been proposed that there should be studies to see if there are any factors to identify which patients are most likely to respond to particular drugs.

Second-line therapy

When a chemotherapy treatment stops working, alternative drugs may be used to try and control the disease further, this is called second-line therapy. Currently in the UK there is no standard second-line therapy, but trials are investigating various potential treatments. There is some evidence to suggest potential benefit from the use of oxaliplatin and 5-FU in patients who have previously received treatment with gemcitabine

In combination with radiotherapy - chemoradiotherapy

This is where a chemotherapy drug is administered in the normal way and at the same time a daily dose of radiotherapy is given. The chemotherapy drugs make the cancer cells more susceptible to radiotherapy.

Currently there is no standardised treatment that uses a combination of chemotherapy and radiotherapy (click here for details about radiotherapy) in the treatment of pancreatic cancer. Indeed recent trials suggest that chemoradiotherapy has not been proved to improve survival rates. There have been several trials conducted worldwide and the results have been inconclusive. If you are offered this treatment, it will almost certainly be part of a clinical trial such as SCALOP which is recruiting patients until December 2011.

Before surgery
This is called preoperative or neoadjuvant therapy and is a recent development in the treatment of pancreatic cancer. It may be offered where the tumour is considered a borderline candidate for surgery. It is possible that a course of chemotherapy has the potential to shrink the tumour sufficiently so that surgery can be performed.

Side-effects of chemotherapy

Most chemotherapy will have some side-effects, and you should let your oncology team know once these develop so they can provide help and support. The type of side effects experienced and their intensity varies between patients. Generally chemotherapy can make you feel tired and this means you have to do things at a slower pace. The specific side-effects of gemcitabine, flurouracil (5FU), and FOLFIRINOX are given below as this is the drug most commonly used in the UK for treating pancreatic cancer.

Gemcitabine - Gemzar

  • Feeling sick or vomiting
  • Swelling of ankles or feet or weight gain due to fluid retention
  • Flu like symptoms
  • Increased risk of infection
  • Skin rash

Fluorouracil - 5FU

  • Diarrhoea
  • Mouth ulcers
  • Hair thinning or hair loss
  • Suppression of the immune system and an increased risk of infection
  • Reddening of the hands and feet

FOLFIRINOX

  • Diarrhoea
  • Hair thinning or hair loss
  • Tingling and numbness of fingertips and toes
  • Can affect full blood count


Chemotherapy drugs used to treat pancreatic cancer

  • Gemcitabine - standard treatment for advanced pancreatic cancer. It is now also used for adjuvant therapy (ie after surgery) and it is also sometimes used in combination with radiotherapy.
  • Capecitabine (Xeloda) - sometimes given in combination with gemcitabine for advanced pancreatic cancer. Also sometimes used as second line therapy or as a sensitizer for radiotherapy.
  • Fluorouracil(5FU) - used for adjuvant therapy, also used to sensitize radiotherapy and sometimes as second line treatment for advanced pancreatic cancer.
  • Cisplatin - somtimes given in combination with gemcitabine for advanced pancreatic cancer
  • Oxaliplatin - somtimes given in combination with gemcitabine for advanced pancreatic cancer

Other drugs which may be used in the treatment for pancreatic cancer:

  • Cetuximab(Erbitux) - a monoclonal antibody that has recently been trialled in combination with chemotherapy such as gemcitabine and cisplatin
  • Tarceva(Erlotinib) - a cancer growth inhibitor that was recently trialled in Canada in combination with gemcitabine and shown to have extra benefit. It has also been included in trials with other therapies.
  • Bevacizumab(Avastin) - a monoclonal antibody. It has been included in recent trials to treat advanced pancreatic cancer.

Drugs used to treat pancreatic cancer worldwide:

  • Gemcitabine (Gemzar)
  • Fluorouracil (5FU)
  • Capecitabine (Xeloda) - an oral drug that is turned into 5FU by your body
  • Erlotinib (Tarceva)
  • Cisplatin
  • Oxaliplatin
  • Other drugs being evaluated in the treatment of pancreatic cancer: Docetaxel(Taxotere), Bevacizumab(Avastin), Cetuximab(Erbitux), Celecoxib, Epirubicin, ALIMTA(pemetrexed), triacetyluridine, ARQ501, glufosfamide, dalteparin, Virulizin, Paclitaxel, 3-AP, Opiod Growth Factor, MDX-010, Sorafenib, GV1001, Curcumin, interferon-alfa, Irinotecan, Thalidomide, Orathecin(Rubitecan or RFS2000), Talabostat, Cyclophosphamide, PANVAC™-VF Vaccine, Survivin Peptide Vaccination, TNFerade

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