Chemotherapy
 
Sometimes your multi-disciplinary team will decide that surgery is unlikely to be an option for you, or that it could be an option at a later date but further exploration/treatment is needed first.
 
Combinations of surgery, chemotherapy and precision medicines are increasingly successful ways of treating a greater number of patients with bowel cancer metastases.
 
The purpose of these types of treatments is to shrink the tumours down and kill the cancer cells, to either make them dormant, or to bring them to a point where they can be removed with surgery, or safely targeted with other kinds of treatment directly into them.
 
The standard chemotherapy drugs for metastases are the same as the ones used to treat cancer in the bowel (colon or rectum).  They can be given on their own, in different combinations at the same time, or given one after the other, depending on your own particular circumstances.  
 
You may recognise some of the names of the individual drugs: Eloxatin (Oxaliplatin), (Camptosar) Irinotecan, 5-FU (5-fluorouracil) and Xeloda (Capecitabine).  
 
These are some of combinations currently being used:

  • FOLFOX (5-FU + Oxaliplatin)
  • FOLFIRI (5-FU + Irinotecan)
  • FOLFOXIRI (5-FU + Oxaliplatin + Irinotecan)
  • XELOX (Capecitabine + Oxaliplatin)
With the exception of the capecitabine capsules, all these drugs are given as infusions.
 
Please visit our Chemotherapy Explained webpage for details on these treatment options.
 

Lonsurf
 
At what stage is this treatment used?
 
Lonsurf (trifluridine and tipiracil) tablets, is used to treat cancer by slowing down the growth and spread of cancer cells.
 
Lonsurf is used to treat adults with metastatic bowel cancer who have previously been treated with other treatments that have not worked or when other treatments are not suitable.
 
Lonsurf is a type of chemotherapy which belongs to a group of medicines called 'cytostatic antimetabolite medicines'.
 
 
Is this drug available via the Pharmaceutical Benefits Scheme (PBS) as a subsidised treatment?
 
  • Lonsurf has been approved by the Therapeutic Goods Administration (TGA) for use in Australia, however, it is not currently listed on the PBS as a subsidised treatment.

Download the Consumer Medicine Information (CMI) for Lonsurf.


Precision medicines explained 

In 2014, the US Food and Drug Administration (FDA) began to approve precision medicines, also known as personalised, targeted or biological therapies for the treatment of cancer.

These treatments work in a variety of ways, including blocking receptors that send growth and survival signals into cells or engaging the body’s immune system to fight cancer cells and have revolutionised cancer treatment.

Initially, therapies targeted the specific proteins vascular endothelial growth factor (VEGF), but now the latest therapies target multiple growth factors and pathways.  

Today, there are three types of antiangiogenic therapies for treating metastatic bowel cancer - antibody, fusion protein, and tyrosine kinase inhibitor - that are available in three lines of therapy.

The development of precision medicine is an exciting step in the treatment of metastatic bowel cancer as it may make it possible to destroy cancer cells without damaging other, healthy cells.

As a result, precision medicine makes it possible for your oncologist to tailor your treatment program to:

  • reduce side effects 
  • extend survival, and 
  • limit toxicity exposure
These new treatments may:

  • stop cancer cells from dividing and growing
  • seek out cancer cells and kill them
  • encourage the immune system to attack cancer cells
  • alter the growth of blood vessels into the tumour
There is no simple way of grouping these treatments.  Some are grouped according to the effect they have, for example: drugs that block cancer cell growth (called EGFR inhibitors) or drugs that block the growth of new blood vessels to the tumour (VEGF inhibitors).
 
The epidermal growth factor receptor (EGFR) is a molecule identified on cancer cells that contributes to tumor development and growth.  In about 80% of malignant bowel cancer tumors, EGFR signaling plays a role in the progression of the disease.  EGFR also can cause angiogenesis.  Anti-EGFR treatment targets this receptor to interrupt its signaling and, thus, hinder tumor development.
 
Some of these drugs can also be called monoclonal antibodies because they target specific proteins on cancer cells.
 
New drugs are being developed which act in different ways and may have multiple modes of action.  
 
Treatment Targeted Therapies

 
 
 
Precision medicines work by interfering with the way individual cancer cells behave so that they cannot thrive or reproduce properly.
 
Used in combination with standard chemotherapy treatments, they can offer a very effective treatment option for some bowel cancer patients.
 
There are currently a number of targeted therapies available for use in Australia to treat metastatic bowel cancer which are outlined below
 
Your oncologist will be able to discuss the possibilities for treatment with you, depending on your own particular circumstances.
 
For more information about chemotherapy and precision medicines please refer to Bowel Cancer Australia's Bowel Cancer - Surgery & Treatment and Advanced Bowel Cancer - Surgery & Treatment resources. 

Avastin (Bevacizumab)
 

At what stage is this treatment used?

Bevacizumab (Avastin) is an antibody drug that binds to and neutralizes a protein called VEGF-A.

It is effective as first-line treatment for metastatic bowel cancer and is used in combination with chemotherapy.

The drug is also approved as part of second line treatment in combination with chemotherapy.

Patients receive bevacizumab as an intravenous infusion every two weeks and can be scheduled on the same day that chemotherapy is given.

Patients may continue bevacizumab even after stopping chemotherapy, as long as the disease is controlled and side effects are manageable.

 

Is this drug available via the Pharmaceutical Benefits Scheme (PBS) as a subsidised treatment?

  • Bevacizumab is PBS-subsidised as a treatment option in combination with first-line chemotherapy (i.e. first-line treatment option), of a patient with previously untreated metastatic bowel cancer with a WHO performance status of 0 or 1.
  • Bevacizumab is PBS-subsidised as a treatment option in combination with second-line chemotherapy, of a patient with RAS wild-type metastatic bowel cancer with a WHO performance of 0 or 1, who have been previously treated with PBS-subsidised first-line anti-EGFR antibodies.

Download the Consumer Medicine Information (CMI) for Bevacizumab.


Erbitux (Cetuximab)

At what stage is this treatment used?

Cetuximab is used as a first or second-line treatment option for patients with epidermal growth factor receptor (EGFR)-expressing, RAS wild-type metastatic bowel cancer in combination with chemotherapy.

Cetuximab can also be given as a single agent in patients who have failed or are intolerant to oxaliplatin-based therapy and irinotecan-based therapy.

Before you are prescribed cetuximab, your specialist will test your cancer cells to see if they contain either the normal (wild-type) or mutant forms of genes called RAS.

Cetuximab is used to treat patients who express normal (wild-type) RAS genes.

 

Is this drug available via the Pharmaceutical Benefits Scheme (PBS) as a subsidised treatment?

  • Cetuximab is PBS-subsidised as a treatment in combination with first-line chemotherapy of a patient with RAS wild-type metastatic bowel cancer who does not have progressive disease.
  • Cetuximab is PBS-subsidised as monotherapy or in combination with an irinotecan based therapy, of a patient with a WHO performance status of 2 or less and with RAS wild type metastatic bowel cancer after failure to respond to first-line chemotherapy. The treatment must be the sole PBS-subsidised anti-EGFR antibody therapy for this condition.
  • Patients who have progressive disease on panitumumab are not eligible to receive PBS-subsidised cetuximab. Patients who have developed intolerance to panitumumab of a severity necessitating permanent treatment withdrawal are eligible to receive PBS-subsidised cetuximab.

Download the Consumer Medicine Information (CMI) for Cetuximab.


Vectibix (Panitumumab)

At what stage is this treatment used?

Panitumumab is used as a first or second-line treatment option for patients with epidermal growth factor receptor (EGFR)-expressing, RAS wild-type metastatic bowel cancer in combination with chemotherapy.

Panitumumab can also be given as a single agent in patients who have failed or are intolerant to oxaliplatin-based therapy and irinotecan-based therapy.

Before you are prescribed panitumumab, your specialist will test your cancer cells to see if they contain either the normal (wild-type) or mutant forms of genes called RAS.

Panitumumab is used to treat patients who express normal (wild-type) RAS genes.

 

Is this drug available via the Pharmaceutical Benefits Scheme (PBS) as a subsidised treatment?

  • Panitumumab is PBS-subsidised as a treatment in combination with first-line chemotherapy of a patient with a WHO performance of 0 or 1 and with RAS wild-type metastatic bowel cancer who does not have progressive disease.
  • Panitumumab is PBS-subsidised as monotherapy or in combination with an irinotecan based therapy, of a patient with a WHO performance status of 2 or less and with RAS wild type metastatic bowel cancer after failure to respond to first-line chemotherapy.
  • The treatment must be the sole PBS-subsidised anti-EGFR antibody therapy for this condition. Patients who have progressive disease on cetuximab are not eligible to receive PBS-subsidised panitumumab. Patients who have developed intolerance to cetuximab of a severity necessitating permanent treatment withdrawal are eligible to receive PBS-subsidised panitumumab.

Download the Consumer Medicine Information (CMI) for Vectibix.


Zaltrap (Aflibercept rch)

 
At what stage is this treatment used?
 
Aflibercept (Zaltrap) is a type of targeted drug known as a fusion protein. This drug is designed to target multiple growth factors involved in cancer and angiogenesis, specifically proteins called VEGF-A, VEGF-B and a related protein called placental growth factor (PlGF).
 
Aflibercept is approved for use as treatment in second-line therapy in combination with chemotherapy (FOLFIRI) for metastatic bowel cancer.
 

Is this drug available via the Pharmaceutical Benefits Scheme (PBS) as a subsidised treatment?

  • Aflibercept has been approved by the Therapeutic Goods Administration (TGA) for use in Australia, however, it is not currently listed on the PBS as a subsidised treatment.

Download the Consumer Medicine Information (CMI) for Zaltrap.


Stivarga (Regorafenib)

At what stage is this treatment used?

Regorafenib (Stivarga), a targeted therapy that comes in pill form, is a tyrosine kinase inhibitor (TKI).

This kind of treatment is designed to target cancer cells and the blood vessels feeding them by interfering with chemical signals or pathways inside abnormal cells.

Regorafenib targets the signaling of multiple growth factors involved in tumor angiogenesis, including VEGF receptors, Fibroblast Growth Factor (FGF) receptors, Platelet-Derived Growth Factor (PDGF) receptors, and the angiopoietin receptor TIE-2. Additional targets of regorafenib include RAF, BRAF, RET and KIT.

Regorafenib is approved for treating patients with metastatic) bowel cancer in the third-line setting, after the cancer has progressed or has recurred after multiple treatments. 

Is this drug available via the Pharmaceutical Benefits Scheme (PBS) as a subsidised treatment?

  • Regorafenib has been approved by the Therapeutic Goods Administration (TGA) for use in Australia, however, it is not currently listed on the PBS as a subsidised treatment.

Download the Consumer Medicine Information (CMI) for Stivarga.


Immunotherapy
 
What is cancer immunotherapy?
 
Immunotherapy is treatment that uses certain parts of a person’s immune system to fight diseases such as cancer.
 
This can be done in a couple of ways:
 
  • Stimulating your own immune system to work harder or smarter to attack cancer cells
  • Giving your immune system components, such as man-made immune system proteins

Some types of immunotherapy are also sometimes called biologic therapy or biotherapy.

In the last few decades immunotherapy has become an important part of treating some types of cancer. Newer types of immune treatments are now being studied, and they’ll impact how we treat cancer in the future.

Immunotherapy includes treatments that work in different ways. Some boost the body’s immune system in a very general way. Others help train the immune system to attack cancer cells specifically.

Immunotherapy works better for some types of cancer than for others. It’s used by itself for some of these cancers, but for others it seems to work better when used with other types of treatment.


What the immune system does?

Your immune system is a collection of organs, special cells, and substances that help protect you from infections and some other diseases. Immune cells and the substances they make travel through your body to protect it from germs that cause infections. They also help protect you from cancer in some ways.

The immune system keeps track of all of the substances normally found in the body. Any new substance that the immune system doesn’t recognise raises an alarm, causing the immune system to attack it. For example, germs contain substances such as certain proteins that are not normally found in the human body. The immune system sees these as “foreign” and attacks them. The immune response can destroy anything containing the foreign substance, such as germs or cancer cells.

The immune system has a tougher time targeting cancer cells, though. This is because cancer starts when cells become altered and start to grow out of control. The immune system doesn’t always recognise cancer cells as foreign.

Clearly there are limits on the immune system’s ability to fight cancer on its own, because many people with healthy immune systems still develop cancer. Sometimes the immune system doesn’t see the cancer cells as foreign because the cells aren’t different enough from normal cells. Sometimes the immune system recognises the cancer cells, but the response might not be strong enough to destroy the cancer. Cancer cells themselves can also give off substances that keep the immune system in check.

To overcome this, researchers have found ways to help the immune system recognise cancer cells and strengthen its response so that it will destroy them.


Types of cancer immunotherapy

The main types of immunotherapy now being used to treat cancer include:

  • Monoclonal antibodies: These are man-made versions of immune system proteins. Antibodies can be very useful in treating cancer because they can be designed to attack a very specific part of a cancer cell.
  • Immune checkpoint inhibitors: These drugs basically take the ‘brakes’ off the immune system, which helps it recognize and attack cancer cells.
  • Cancer vaccines: Vaccines are substances put into the body to start an immune response against certain diseases. We usually think of them as being given to healthy people to help prevent infections. But some vaccines can help prevent or treat cancer.
  • Other, non-specific immunotherapies: These treatments boost the immune system in a general way, but this can still help the immune system attack cancer cells.

Immunotherapy drugs are now used to treat many different types of cancer. 


Immunotherapy for Bowel Cancer

An important part of the immune system is its ability to keep itself from attacking the body's normal cells. To do this, it uses 'checkpoint' proteins on immune cells, which act like switches that need to be turned on (or off) to start an immune response.

Cancer cells sometimes use these checkpoints to keep the immune system from attacking them. But drugs that target these checkpoints hold a lot of promise as cancer treatments.

Pembrolizumab (Keytruda) and Nivolumab (Opdivo) are drugs that target PD-1 (programmed cell death protein 1). PD-1 is a protein found on immune system cells called T cells. It normally helps keep these cells from attacking "good" cells in the body.

Pembrolizumab and nivolumab block the cancer cells' ability to attach to PD-1, so, the immune system can then 'see' the cells as 'bad'. This boosts the immune response against the cancer cells and can shrink some tumors or slow their growth.

These drugs can be used for people whose bowel cancer cells have tested positive for specific gene changes, such as a high level of microsatellite instability (MSI-H), or changes in one of the mismatch repair (MMR) genes.

The drugs are used for people whose cancer is still growing after treatment with chemotherapy. They might also be used to treat people whose cancer can't be removed with surgery, has come back (recurred) after treatment, or has spread to other parts of the body (metastasised).

Pembrolizumab (Keytruda) is given as an intravenous (IV) infusion. Treatment takes about 30 minutes and is given every 3 weeks.

Nivolumab (Opdivo) is given as an (IV infusion) that takes one hour. It's given every two weeks.


Keytruda (Pembrolizumab) 

At what stage is this treatment used?

The US Food and Drug Administration (FDA) granted accelerated approval to a treatment for patients whose cancers have a specific genetic feature (biomarker) in May 2017.

This is the first time the agency has approved a cancer treatment based on a common biomarker rather than the location in the body where the tumor originated.

Keytruda (pembrolizumab) is indicated for the treatment of patients with unresectable or metastatic solid tumors that have been identified as having a biomarker referred to as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR).

This indication covers patients with solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options and patients with bowel cancer that has progressed following treatment with certain chemotherapy drugs.

MSI-H and dMMR tumors contain abnormalities that affect the proper repair of DNA inside the cell.

Tumors with these biomarkers are most commonly found in bowel, endometrial and gastrointestinal cancers, but also less commonly appear in cancers arising in the breast, prostate, bladder, thyroid gland and other places.

Approximately five percent of patients with metastatic bowel cancer have MSI-H or dMMR tumors.

Keytruda works by targeting the cellular pathway known as PD-1/PD-L1 (proteins found on the body’s immune cells and some cancer cells). By blocking this pathway, Keytruda may help the body’s immune system fight the cancer cells.

 

Is this drug available via the Pharmaceutical Benefits Scheme (PBS) as a subsidised treatment?

  • Keytruda has not been approved by the Therapeutic Goods Administration (TGA) for use in Australia as a treatment option for bowel cancer, and is not currently listed on the PBS as a subsidised treatment.

Opdivo (Nivolumab) 

At what stage is this treatment used?

In July 2017, the US Food and Drug Administration (FDA) granted accelerated approval to nivolumab (Opdivo) for the treatment of patients twelve years and older with mismatch repair deficient (dMMR) and microsatellite instability high (MSI-H) metastatic bowel cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.

The approval was based on data from Study CA209142, a multicenter, open-label, single arm study conducted in 53 patients with locally determined dMMR or MSI-H metastatic bowel cancer who had disease progression during, after, or were intolerant to prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.

This was a subset of the 74 patients who received at least one prior regimen for treatment of metastatic disease containing a fluoropyrimidine with oxaliplatin or irinotecan for treatment of metastatic disease. All patients received nivolumab 3 mg/kg by intravenous infusion every 2 weeks until unacceptable toxicity or radiographic progression.

 

Is this drug available via the Pharmaceutical Benefits Scheme (PBS) as a subsidised treatment?

Opdivo has not been approved by the Therapeutic Goods Administration (TGA) for use in Australia as a treatment option for bowel cancer, and is not currently listed on the PBS as a subsidised treatment.