Bowel Cancer Just Diagnosed? Surgery & Trea

Shortly after diagnosis and these further tests, you will discuss with your specialist the options open to you, including when and where treatment will take place, the process you will go through, what drugs will be available for your treatment, if required, and who will be treating you at each stage.

The specialist will put together a treatment plan with you.  This is developed depending on a number of factors such as:

• the type and size of the cancer
• what stage the cancer is at
• your personal health condition and age

It is very important to discuss with your doctors the advantages and disadvantages of what is being suggested so that your individual needs may be fully considered.  You may want to know the possible effects of treatments on your fertility or sexual function.  If you are told you will need a colostomy or ileostomy you should be able to discuss this fully before surgery and have an indication of whether it may be reversible.  

Many people with bowel cancer want to take an active part in making decisions about their medical care.  It is natural to want to learn all you can about your disease and treatment choices. However, shock and stress after the diagnosis can make it hard to think of everything you want to ask your doctor.  It often helps to make a list of questions before an appointment.

To help remember what your doctor says, you may take notes.  You may also want to have a family member or friend with you when you talk to your doctor -- to take part in the discussion, to take notes, or just to listen.

You do not need to ask all your questions at once.  You will have other chances to ask your doctor or nurse to explain things that are not clear and to ask for more details.

Your doctor may refer you to a specialist who has experience treating bowel cancer, or you may ask for a referral. 

Health professionals who treat bowel cancer include –

• Gastroenterologists (doctors who specialise in diseases of the digestive system and colonoscopy)
• Surgeons (colorectal surgeons or general surgeons who specialise in bowel cancer) 
• Medical oncologists (responsible for chemotherapy)
• Radiation oncologists (responsible for radiotherapy)
• Dietitians (who recommend best eating plans to follow while you are in treatment and recover) 
• Cancer Care Coordinators (who facilitate the continuity and quality of your care and support you and your family throughout your treatment)

If these health professionals work together to plan your treatment, they become known as your multidisciplinary care team.

Treatment for Colon Cancer

Most patients with colon cancer are treated with surgery.  Some people have both surgery and chemotherapy.  Some with advanced disease receive biological therapy.

A colostomy is seldom needed for people with colon cancer.

Although radiation therapy is rarely used to treat colon cancer, sometimes it is used to relieve pain and other symptoms.

Treatment for Rectal Cancer

For all stages of rectal cancer, surgery is the most common treatment.  Some patients receive surgery, radiation therapy, and chemotherapy.  Some with advanced disease receive biological therapy.

About 1 out of 8 people with rectal cancer need a permanent colostomy.

Radiation therapy may be used before and after surgery.  Some people have radiation therapy before surgery to shrink the tumour, and some have it after surgery to kill cancer cells that may remain in the area.
At some hospitals, patients may have radiation therapy during surgery.  Patients may also have radiation therapy to relieve pain and other problems caused by the cancer.

Getting a Second Opinion

Options in the management of bowel cancer can be complex at times, but are well understood by surgeons who specialise in bowel surgery.
Before starting treatment, you might want a second opinion about your diagnosis and treatment plan.
A second opinion regarding your particular cancer may be recommended by your doctor.
Surgeons who specialise in the management of bowel cancer, and particularly rectal cancer, are members of the Colorectal Surgical Society of Australia and New Zealand.
If your doctor is uncertain, the Soceity can advise regarding members near you.

Treatment Methods

The choice of treatment depends mainly on the location of the tumour in the colon or rectum and the stage of the disease. 

Treatment for bowel cancer may involve surgery, chemotherapy, biological therapy or radiation therapy.  Some people have a combination of treatments.  These treatments are described below.
Colon cancer sometimes is treated differently from rectal cancer.  Treatments for colon and rectal cancer are described separately above.
Your doctor can describe your treatment choices and the expected results.  You and your doctor can work together to develop a treatment plan that meets your needs.
Cancer treatment is either local therapy or systemic therapy:

• Local therapy – surgery and radiation therapy are local therapies.  They remove or destroy cancer in or near the colon or rectum.  When bowel cancer has spread to other part of the body, local therapy may be used to control the disease in those specific areas.
   
• Systemic therapy – chemotherapy and biological therapy are systemic therapies.  The drugs enter the bloodstream and destroy or control cancer throughout the body.

Because cancer treatments often damage healthy cells and tissues, side effects are common. 

Side effects depend mainly on the type and extent of the treatment.  Side effects may not be the same for each person, and they may change from one treatment session to the next.  Before treatment starts, your health care team will explain possible side effects and suggest ways to help you manage them.

You may want to ask your doctor these questions before treatment begins –

• What is the stage of the disease?
• Has the cancer spread?
• What are my treatment choices?
• Which do you suggest for me?
• Will I have more than one kind of treatment?
• What are the expected benefits of each kind of treatment?
• What are the risks and possible side effects of each treatment?
• How can the side effects be managed?
• What can I do to prepare for treatment?
• How will treatment affect my normal activities?
• Am I likely to have urinary problems?
• What about bowel problems, such as diarrhoea or rectal bleeding?
• Will treatment affect my sex life?
• What will the treatment cost?
• Is this treatment covered by my private health insurance?

Surgery

Unlike some other cancers where many treatment choices are available, surgery is the most common treatment for removing the cancer from your bowel.

However, some people will also require chemotherapy and radiotherapy to reduce the size of the tumour and prevent progression of the disease.  If surgery is not an option, then chemotherapy and radiotherapy are offered to halt progression of the disease and to help control the symptoms.


What happens during surgery?

During the operation the piece of bowel that contains the cancer is removed and the two open ends are joined together.  The lymph nodes near the bowel may also be removed because this is the first place to which the cancer may spread.

You will usually stay in hospital for about 10 days after surgery, and will be given antibiotics to prevent any infection.

You may want to ask your doctor these questions before having surgery –

• What kind of operation do you recommend for me?
• Do I need any lymph nodes removed? 
• Will other tissues be removed? 
• Why?
• What are the risks of surgery? 
• Will I have any lasting side effects?
• Will I need a colostomy? 
• If so, will the stoma be permanent?
• How will I feel after the operation?
• If I have pain, how will it be controlled?
• How long will I be in the hospital?
• When can I get back to my normal activities?

Colon cancer surgery with anastomosis. Part of the colon containing the cancer and nearby healthy tissue is removed,
and then the cut ends of the colon are joined.  Image courtesy of the National Cancer Institute.

Will you need a colostomy bag?

Most people diagnosed with bowel cancer do not need a colostomy bag.  However, in some cases, the bowel cannot be rejoined straight away, and one end if brought out onto the skin of the abdominal wall.  This is called a colostomy, and the opening of the bowel is known as a stoma.  Bowel motions pass through the stoma into a colostomy bag, which is worn over the stoma.

For most people, the stoma is temporary and can be reversed after a few months.  It is needed only until the colon or rectum heals from surgery.  After healing takes place, the surgeon reconnects the parts of the bowel and closes the stoma. 

Only a very small number of people with bowel cancer cannot have a stoma reversal.  Some people, especially those with a tumour in the lower rectum, need a permanent stoma.

If you do need a colostomy bag after surgery, you will be given support and advice from specialist stoma care nurses.  People who have a colostomy bag may have irritation of the skin around the stoma.  Your doctor or nurse can teach you how to clean the area and prevent irritation and infection.  Life can carry on as normal with a stoma, including sporting activities.

Colon cancer surgery with colostomy. Part of the colon containing the cancer and nearby healthy tissue is removed,
a stoma is created, and a colostomy bag is attached to the stoma.  Image courtesy of the National Cancer Institute.
 

Open surgery or keyhole surgery?

Open surgery is currently the most common form of surgery for bowel cancer patients.  In the majority of cases, open surgery to remove bowel cancer is highly successful and can be completely curative if the cancer is caught at an early enough stage.

After open surgery you will have a wound (incision) that goes in a straight line from just below the breastbone for a variable length down to the pelvis.  However, this scar will heal and fade over time.  You can expect to be in hospital for an average of 8-10 days.

The time it takes to heal after surgery is different for each person.  You may be uncomfortable for the first few days.  Medicine can help control your pain.  Before surgery, you should discuss the plan for pain relief with your doctor or nurse.  After surgery, your doctor can adjust the plan if you need more pain relief.

It is common to feel tired or weak for a while.  Also, surgery sometimes causes constipation or diarrhoea.  Your health care team monitors you for signs of bleeding, infection, or other problems requiring immediate treatment.

National Health & Medical Research Council guidelines recommend laparoscopic (or keyhole) surgery, in experienced hands, as a safe and feasible alternative to open surgery for benign bowel cancer.

The decision about whether to use open or laparoscopic surgery should be made after informed discussion between the patient and the surgeon.  In particular, they should talk about whether the patient’s condition is suitable for laparoscopic surgery, the risks and benefits of the two procedures, and he surgeon’s experience.

Laparoscopic surgery involves carrying out an operation through small cuts in the abdomen.  This type of procedure is often called keyhole surgery.  The surgeon inserts a narrow telescope attached to a camera and other special instruments through the cuts to remove the part of the bowel with the tumour.  Most of the operation is performed through these small cuts, but a slightly larger opening is needed to remove the section of bowel from the body.

Laparoscopically assisted surgery is similar, but involves using the larger opening to carry out part of the surgery as well as to remove the section of bowel.  Both procedures need smaller cuts than open surgery. 

Radiotherapy

Radiotherapy (also called radiation therapy) uses high-energy rays to kill cancer cells.  It works by destroying the cancer cells in the treated area, and can be given before or after surgery.  Sometimes radiotherapy and chemotherapy are given at the same time.

Doctors use different types of radiation therapy to treat cancer.  Sometimes people receive two types –

• External radiation – the radiation comes from a machine.  The most common type of machine used for radiation therapy is called a linear accelerator.  Most patients go to the hospital or clinic for their treatment, generally 5 days a week for several weeks.
   
• Internal radiation (implant radiation or brachytherapy) – the radiation comes from radioactive materials placed in thin tubes put directly into or near the tumour.  The patient stays in the hospital, and the implants generally remain in place for several days.  Usually they are removed before the patient goes home.
   
• Intraoperative radiation therapy (IORT) – in some cases, radiation is given during surgery.   

Will you suffer from side effects?

Radiotherapy can destroy cancer cells, but it can also have an effect on some of the surrounding normal cells.

Side effects depend mainly on the amount of radiation given and the part of your body that is treated.  Radiation therapy to your abdomen and pelvis may cause nausea, vomiting, diarrhoea, bloody stools, or urgent bowel movements.  It also may cause urinary problems, such as being unable to stop the flow of urine from the bladder.  In addition, your skin in the treated area may become red, dry, and tender. The skin near the anus is especially sensitive.

You are likely to become very tired during radiation therapy, especially in the later weeks of treatment.  Resting is important, but doctors usually advise patients to try to stay as active as they can.

Although the side effects of radiation therapy can be distressing, your doctor can usually treat or control them.  Also, side effects usually go away after treatment ends.

You may want to ask your doctor these questions about radiation therapy –

• Why do I need this treatment?
• When will the treatments begin? 
• When will they end?
• How will I feel during treatment?
• How will we know if the radiation treatment is working?
• What can I do to take care of myself during treatment?
• Can I continue my normal activities?
• Are there any lasting effects?

Chemotherapy

Chemotherapy uses anti-cancer drugs to kill cancer cells.  The drugs enter the bloodstream and can affect cancer cells all over the body.

Chemotherapy is used at several different stages of treatment –

• ‘Neo-adjuvant’ – to shrink the tumour(s) before surgery in order to get a better outcome following the operation.
  
   
• ‘Adjuvant’ – to destroy any microscopic cancer cells that may remain after the cancer is removed by surgery and reduce the possibility of the cancer returning.
  
   
• 'First-line' – chemotherapy that has been shown, through extensive clinical trails and research, to be the best option for the type of cancer being treated.
  
   
• 'Second-line' – chemotherapy that has been shown, through extensive clinical trials and research, to be the best option if the disease has not responded to first-line chemotherapy or has recurred.
  
   
• 'Palliative' – to relieve symptoms and slow the spread of the cancer, if a cure is not possible.

In order for the chemotherapy to destroy cancer cells in the body, the drugs have to be absorbed into your blood and carried throughout your body.

The chemotherapy drugs can be given in different ways, for example -

• Oral chemotherapy – if your chemotherapy drug is available as a tablet which you swallow, this can be taken at home.  You would only need to go to the hospital for routine outpatients' appointments, which would include a blood test.  As oral chemotherapies can cause side effects it is important to be aware of these and report them to your medical team immediately.
   
• Intravenous (IV) injection – the treatment is injected into a vein - either over a few minutes, up to 30 minutes, or over the course of a couple of hours.  IV chemotherapy can be given via 4 different methods:
   
  1. Cannula: a small tube inserted into a vein in the back of your hand, or your arm.
     
      
  2. Central Line: a thin, flexible tube inserted though the skin of the chest into a vein near the heart.
     
      
  3. PICC Line (a peripherally inserted central catheter): a thin, flexible tube passed into a vein in the bend or upper part of your arm and threaded through the vein until the end of the tube lies in a vein near the heart.  PICC lines can stay in place for many months.
     
      
  4. Portacath: a thin, soft plastic tube that is put into a vein.  It has an opening (port) just under the skin on your chest or arm.

If your oncologist believes you will benefit from chemotherapy, they will discuss the proposed treatment plan with you.  You may be prescribed one drug or a combination of drugs.  Ask your specialist about what they are recommending for you, how the chemotherapy will be given and the choices you have.

The side effects of chemotherapy depend mainly on the specific drugs and the dose. The drugs can harm normal cells that divide rapidly –

• Blood cells – these cells fight infection, help blood to clot, and carry oxygen to all parts of your body.  When drugs affect your blood cells, you are more likely to get infections, bruise or bleed easily, and feel very weak and tired.
  
   
• Cells in hair roots – chemotherapy can cause hair loss.  Your hair will grow back, but it may be somewhat different in colour and texture.
  
   
• Cells that line the digestive tract – chemotherapy can cause poor appetite, nausea and vomiting, diarrhoea, or mouth and lip sores. 

Chemotherapy for bowel cancer can cause the skin on the palms of the hands and bottoms of the feet to become red and painful.  The skin may peel off.

Your health care team can suggest ways to control many of these side effects.  Most side effects usually go away after treatment ends.

You might want to ask your oncologist these questions before having chemotherapy therapy –

• What drugs will I have? 
• What will they do?
• When will treatment start? 
• When will it end? 
• How often will I have treatments?
• Where will I go for treatment? 
• Will I be able to drive home afterward?
• What can I do to take care of myself during treatment?
• How will I know the treatment is working?
• Which side effects should I tell you about?
• Will there be long-term side effects?

Side effects
Because chemotherapy kills dividing cells,which might be cancerous, it can also affect parts of your body where normal cells divide frequently, such as the mouth, hair, bone marrow and so on.
The risk of side effects depends on the drugs used and the dose you need.  You should talk to your specialist or chemotherapy nurse about side effects and should be given written information about the dif­ferent drugs.  Then try to weigh up the side effects against the overall benefits of the treatment.
Cancer-related anaemia and the fatigue associated with it has a profound impact on patient's lives, yet it is still commonly under-diagnosed and under-treated.  Chronic fatigue in bowel cancer may be caused by the chemotherapy or radiotherapy, or by surgery.  If you are experiencing this, talk to your specialist - it can be treated.  You may be offered a blood transfusion, or a treatment called EPO which you can take as a simple injection at home.

Availability of drugs

In Australia there are a number of government bodies responsible for the regulation and availability of bowel cancer treatments.
The Therapeutic Goods Act 1989, Regulations and Orders provide a national framework for the regulation of therapeutic goods in Australia to ensure quality, safety and effectiveness of medicines.  They also set out the requirements for inclusion of therapeutic goods in the Australian Register of Therapeutic Goods (ARTG), including advertising, labelling and product appearance, for example.
The Therapeutic Goods Administration (TGA) is a unit of the Australia Government Department of Health and Ageing.  It carries out a range of assessment and monitoring activities to ensure therapeutic goods available in Australia are of an acceptable standard.  At the same time the TGA aims to ensure that the Australian community has access, within a reasonable time, to therapeutic advances.
All treatments used to prevent, cure or alleviate bowel cancer must be entered on the Australian ARTG before they can be supplied in Australia.  Once approved and entered on the ARTG, they are available for human use and can be accessed privately.
Some treatments can then be recommended by the Pharmaceutical Benefits Advisory Committee (PBAC) to be listed on the Pharmaceutical Benefits Scheme (PBS) as a subsidised treatment.  The Scheme is available to all Australian residents who hold a current Medicare card.
The PBAC is an independent statutory body established to make recommendations and give advice to the Minister for Health & Ageing about which treatments should be made available as pharmaceutical benefits.
No new treatment may be made available as a pharmaceutical benefit unless the Committee has so recommended.
The Committee is required by the National Health Act 1953 to consider the effectiveness and cost of a proposed benefit compared to alternative therapies.  In making its recommendations the Committee, on the basis of community usage, recommends maximum quantities and repeats and may also recommend restrictions as to the indications where PBS subsidy is available.
When recommending listings, the Committee provides advice to the Pharmaceutical Benefits Pricing Authority (PBPA) regarding comparison with alternatives or their cost effectiveness.
Some treatments may not be recommended by the PBAC if they are deemed not cost-effective, even if they are clinically proven.
The issue of drug availability has received a lot of media attention and can be confusing and complicated.  You should discuss all the options with your oncologist, and if a drug would be of benefit but it is not available via the PBS, you may consider accessing this privately or applying to a manufacturer to see if you are eligible to enter an access program or the drug made available on compassionate grounds.
Also, ask about clinical trials.
A list of the applications for consideration at each PBAC meeting is published six(6) weeks prior to each meeting.  The sponsor of the submission will have already provided the PBAC with detailed clinical and economic data in support of the submission.  However, you are welcome to provide comments from a personal (i.e. patient, carer, member of the public, health professional) or group perspective for consideration by the PBAC when the submission is considered.
Further details, including closing dates for input, can be found at www.health.gov.au.
In 25 May 2011 the Minister for Health and Ageing confirmed on Hansard that the Government is "concentrating on listing medicines on the PBS that treat serious and life threatening conditions where there are no alternative treatments on the PBS."
In doing so, the Government will rely "upon information provided by the PBAC in relation to clinical need for each medicine or vaccine, including whether alternative treatment options exist, and whether there were comparable listings in the past three years.  Additional information taken into account is whether the listing provides expenditure savings and other technical information that the PBAC considered.  The Government also relies on the expert advice from the Department of Health and Ageing and the Chief Medical Officer."
Any PBS listings with a financial impact will now have to be considered by Cabinet.

Performance status

Doctors use the WHO performance status to describe how well you are.  They also call it your ‘performance status'.  The World Health Organisation designed the scale that doctors use most often.  It has categories from 0 to 4.  Here is what they mean –

 

• 0 – you are fully active and more or less as you were before your illness

• 1 – you cannot carry out heavy physical work, but can do anything else

• 2 – you are up and about more than half the day; you can look after yourself, but are not well enough to work

• 3 – you are in bed or sitting in a chair for more than half the day; you need some help in looking after yourself

• 4 – you are in bed or a chair all the time and need a lot of looking after

 

Clinical trials often include performance status as one of the criteria you must meet to join the trial as researcher have to make sure people are well enough to take part.

 

Similarly, a patient’s WHO performance status is often a criteria you must meet to be eligible for some PBS-subsidised bowel cancer treatments.

 

 

Chemotherapy drugs

Chemotherapy treatment for bowel cancer is improving dramatically.  Although the most common chemotherapy is 5-fluorouracil (5-FU) which has been the main treatment for over 40 years, there have been several new drugs developed to help fight bowel cancer which have improved the results set by 5-FU.
Frequently, two or more chemotherapy drugs are given together.  This is known as combination therapy.  Studies have shown that patients receiving combination therapy have significant advantages both in response rate and survival.  Sometimes monoclonal antibodies are added to chemotherapy to further improve the results. 

Treatment	At what stage is this treatment used?	Is this treatment PBS subsidised?	Click to download Consumer Medicine Information (CMI)
5-Fluorouracil (5-FU)	At any stage of bowel cancer.  It is usually combined with folinic acid (Leucovorin Calcium).	Yes.
Oxaliplatin (Eloxatin)	Adjuvant treatment of stage III (Dukes C) colon cancer after complete resection of primary tumour.    Treatment of metastatic colorectal cancer.	Oxaliplatin in combination with 5-FU and folinic acid (FOLFOX) is PBS-subsidised as a treatment option for the adjuvant treatment of patients with stage III (Dukes C) colon cancer following complete resection of the primary tumour.    Oxaliplatin in combination with 5-FU and folinic acid (FOLFOX) or capecitabine (XELOX) is PBS-subsidised as a treatment option for metastatic colorectal cancer in patients with a WHO performance status of 2 or less.   Oxaliplatin is not PBS-subsidised for the treatment of patients with stage II (Dukes B) colon cancer.  Oxaliplatin is not PBS-subsidised for the adjuvant treatment of patients with rectal cancer.   From 1 December 2011, capecitabine in combination with oxaliplatin (XELOX) will be listed as a PBS-subsidised treatment option for the adjuvant treatment of stage III (Dukes C) colon cancer.  This latest recommendation will allow Xeloda to be reimbursed as both monotherapy and as part of the XELOX combination.
Capecitabine (Xeloda)	Adjuvant treatment of stage III (Dukes C) colon cancer.  Treatment of advanced or metastatic bowel cancer alone or in combination.	Capecitabine is PBS-subsidised as a treatment option for advanced or metastatic colorectal cancer.  It is also PBS-subsidised as a treatment option for adjuvant treatment of stage III (Dukes C) colon cancer, following complete resection of the primary tumour. Capecitabine is not PBS-subsidised for the treatment of patients with Stage II (Dukes B) colon cancer.  Capecitabine is not PBS-subsidised for the adjuvant treatment of patients with rectal cancer. From 1 December 2011, capecitabine in combination with oxaliplatin (XELOX) will be listed as a PBS-subsidised treatment option for the adjuvant treatment of stage III (Dukes C) colon cancer.  This latest recommendation will allow Xeloda to be reimbursed as both monotherapy and as part of the XELOX combination.
lrinotecan (Camptosar)	1st line combination and 2nd line monotherapy treatment of advanced colorectal cancer.	Irinotecan is PBS-subsidised as a treatment option for metastatic colorectal cancer in patients with a WHO performance status of 2 or less. Note: In first-line usage, effectiveness and tolerance may be improved when Irinotecan is combined with an infusional 5-fluorouracil regimen (e.g. FOLFIRI).

 

KRAS testing

Scientists now understand that bowel cancer starts when the building "blue print" (the genes) for individual cells in the bowel are damaged and changed in some way.
Understanding how these abnormal cells behave means that doctors now also increasingly understand how the new cancer medicines available will work when bowel cancer spreads to other parts of the body.
They may be able to select an individual treatment plan for you that will have a better chance of success.  Importantly, they may also be able to avoid giving you medicines if they know they won't work.

When would I have a KRAS test done?
Changes to the genes, identified as KRAS, usually happen slowly, in stages, to the same gene in the affected cells.  The KRAS change occurs first, and is a useful marker when deciding which patients will respond to certain treatments for bowel cancer that has spread to other parts of the body.
If your bowel cancer has spread only to your liver and your liver surgeon believes that these tumours could be removed by surgery, then you should have this test done automatically.
You may also be able to ask to have the test done, if you have both liver metastases that can be removed and another limited area of potentially treatable, secondary disease.
Secondary bowel cancer can be treated with a range of medicines called monoclonal antibodies.
KRAS testing does not affect the way your chemotherapy is prescribed.  Instead, it gives your oncologist the information they need to work out which other medicine from the monoclonal antibodies group may work for you.
Some monoclonal antibodies are given at the same time as your chemotherapy, whilst others are given on their own.

How are the tests done?
These tests are usually done on the cancer cells from the tumour or biopsy that was removed during your operation or endoscopy.  Samples of the cancer will have been preserved and stored in the hospital laboratory.  Your medical team will arrange for this tissue sample to be tested, which will confirm whether your tumour is -

• Wild-type  KRAS (also called  'normal')
• Mutated KRAS  

How long do the test results take to come back?

 

Once the tissue sample has been located, the test results typically take 5-7 working days to come back to your oncologist.

 

What are the treatment options once the KRAS status is known?

 

Monoclonal antibodies are a group of drugs which work to stop the cancer cells growing and developing by interfering with their reproduction processes (anti-EGFR) or by cutting off their blood supply (anti-VEGF). 

 

Up to 60% of bowel cancer tumours do not carry the KRAS gene mutation.  These tumours are commonly referred to as KRAS wild-type.  Clinical studies have shown that tumours which are KRAS wild-type can be successfully treated with anti-EGFR monoclonal antibodies cetuximab (Erbitux) and panitumumab (Vectibix), as well the anti-VEGF monoclonal antibody bevacizumab (Avastin).

Around 40% of bowel cancer tumours that carry the KRAS gene mutation are referred to as KRAS positive tumours.  Clinical studies have shown that patients with KRAS positive tumours may be successfully treated with the anti-VEGF therapy bevacizumab (Avastin), but do not respond to anti-EGFR therapy.  

Monoclonal Antibodies

Some people with bowel cancer that has spread receive a monoclonal antibody, a type of biological therapy and are a different type of treatment to chemotherapy.

• ‘Monoclonal’ means all one type.
   
• ‘Antibody’ is a protein in your immune system that recognises and attacks foreign substances.

So a ‘monoclonal antibody’ is a treatment designed to recognise and target only one type of foreign substance (e.g. cancer cells).

The development of monoclonal antibody treatments is an exciting development in the treatment of cancer as it may be possible to kill cancer cells without damaging other healthy cells.

The monoclonal antibodies bind to bowel cancer cells.  They interfere with cancer cell growth and the spread of cancer.  People receive monoclonal antibodies through a vein at the doctor's office, hospital, or clinic.  Some people receive chemotherapy at the same time.

During treatment, your health care team will watch for signs of problems.  Some people get medicine to prevent a possible allergic reaction.  The side effects depend mainly on the monoclonal antibody used.  Side effects may include rash, fever, abdominal pain, vomiting, diarrhoea, blood pressure changes, bleeding, or breathing problems.  Side effects usually become milder after the first treatment.

Monoclonal Antibody Treatments for Advanced Bowel Cancer

There are three Monoclonal Antibody (MAB) treatments for bowel cancer -

• Bevacizumab (Avastin)
• Cetuximab (Erbitux)
• Panitumumab (Vectibix)

These treatments seek out cancer cells that produce too much of a particular growth factor (a substance which stimulates a cell to grow and divide) and block the cell's receptors so the cell can't receive the signal to grow.

Treatment	At what stage is this treatment used?	Is this treatment PBS-subsidised?	Click to download Consumer Medicine Information (CMI)
Bevacizumab (Avastin)	Used for first and later treatment lines of advanced or metastatic colorectal cancer in combination with a fluoropyrimidine based chemotherapy.  Use of bevacizumab is not dependent on KRAS status.	In July 2008, bevacizumab was recommended for PBS listing by the PBAC. On 1 July 2009, Bevacizumab was added as an initial PBS-subsidised treatment, in combination with first-line chemotherapy, of a patient with previously untreated metastatic colorectal cancer with a WHO performance status of 0 or 1. Bevacizumab is also listed as a continuing PBS-subsidised treatment, in combination with first-line chemotherapy, of a patient with metastatic colorectal cancer who has previously been issued with an authority prescription for bevacizumab and who does not have progressive disease and who remains on first-line chemotherapy.  Bevacizumab is not for use as monotherapy.
Cetuximab(Erbitux)	Used for the treatment of patients with epidermal growth factor receptor (EGFR)-expressing, KRAS wild-type advanced or metastatic colorectal 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.	In July 2010, cetuximab was recommended for PBS listing by the PBAC. On 1 September 2011, cetuximab was added as an initial PBS-subsidised treatment, as monotherapy or in combination with an irinotecan based therapy, of a patient with a WHO performance status of 2 or less and with K-RAS wild type metastatic colorectal cancer after failure of first-line chemotherapy. Cetuximab was also listed as a conitnuing PBS-subsidised treatment, as monotherapy or in combination with an irinotecan based therapy, of a patient with K-RAS wild type metastatic colorectal cancer who has previously been issued with an authority prescription for cetuximab and who does not have progressive disease.   Cetuximab is not PBS-subsidised for use in combination with bevacizumab or oxaliplatin based therapies.
Panitumumab (Vectibix)	As monotherapy for the treatment of patients with EGFR-expressing metastatic colorectal carcinoma with non-mutated (wild-type) KRAS after failure of irinotecan and oxaliplatin containing regimens.	In November 2008, the PBAC rejected a submission to add Panitumumab to the list of subsidised drugs under the PBS for patients with advanced bowel cancer, citing uncertain clinical benefit and the resultant high and highly uncertain cost effectiveness.  The (unsibsidised) drug is available privately to patients via their oncologist.

You might want to ask your oncologist these questions before having biological therapy –

• What drugs will I have?
• What will they do?
• When will treatment start?
• When will it end?
• How often will I have treatments?
• Where will I go for treatment?
• Will I be able to drive home afterward?
• What can I do to take care of myself during treatment?
• How will I know the treatment is working?
• Which side effects should I tell you about?
• Will there be long-term side effects?

Improving the lives of patients with bowel cancer through recognition of the value of prolonged, quality of life is one of the aims of the Bowel Cancer 2012 Challenge, presented to Government on 7 May 2009.
 

Clinical Trials

What is a clinical trial?

Clinical trials are carefully designed and regulated research studies.

Clinical trials are essential for improving cancer care.  They help to determine whether new cancer treatments, diagnostic tests or preventive interventions are effective, and identify best practice cancer care.
Are there different types of trials?

• Diagnosing trials evaluate ways of detecting certain types of disease.
   
• Prevention trials can either be ‘action studies’ e.g.: does exercising three times a week reduce your risk of cancer, or ‘agent studies’ e.g.: does taking a certain vitamin reduce your risk of cancer.
   
• Quality of life trials can measure an individual’s sense of well-being and quality of life during treatment.
   
• Screening trials can find new methods of screening for cancer which would mean that more cases could be diagnosed at an earlier stage.
   
• Treatment trials look at new ways of treating and managing a specific condition.

Why are clinical trials needed in cancer?

Carrying out clinical trials is the only way to find out if a new approach is better than the approach currently being used and can include –

• Testing new treatments, e.g. new drugs or ways of giving treatment.
   
• Examining new combinations of treatments, or when/how they are given.
   
• Looking at the effect of different treatments, such as psychological or complementary therapy.
   
• Discovering which treatments cause which side effects, and how these can be managed.
   
• Investigating the convenience of different treatments (e.g. oral tablets versus intravenous injections).
   
• Studying whether treatment (for example, chemotherapy) should be given before or after surgery.

Treatment Trials

What are the different phases of treatment trials?

Treatment trials go through a series of ‘phases’ to test whether they are safe and if they work. All new cancer drugs are tested in the laboratory before they are given to people in trials.

Phase 1 trials involve a small number of people, in a specialist research unit, and aim to discover appropriate doses, the effect the drugs have on the body, side effects etc. Researchers start with very small doses and only increase the amount given if the participants experience no or minor side effects.  If the drug is effective and a safe dose is found following a number of phase 1 trials, it will progress to phase 2 trials.

Phase 2 trials, still involving a small number of patients, aim to discover on what types of cancer the treatment is most effective, the side effects, the best dose, and if larger, more extensive phase 3 studies would be appropriate.  Throughout these studies patients are very closely monitored.  Sometimes phase 2 trials may include testing the best way to give a treatment, for example by tablet or injection.

Phase 3 trials aim to compare the effectiveness of the new treatment with current, standard treatment and only start when the treatment has successfully passed through phase 1 and 2 trials.  This phase provides more information on outcomes and side effects.  These trials often last a year or more, and can include hundreds or thousands of patients, from different hospitals, often across several countries.  Phase 3 trials always involve randomisation (see below for details).

Phase 4 trials are carried out after a drug has received a license (meaning doctors can prescribe it outside of trials) and has been demonstrated to be effective.  The studies further investigate long term risks/side effects and how the treatment works outside of clinical trial environments.  Phase 4 studies are not required for every medicine.

What is randomisation?

‘Randomisation’ is a way that a patient is assigned within the trial to either receive the ‘trial’ treatment or the standard ‘best currently available’ treatment.  Randomisation works by chance, is done via a computer, and means that each patient has an equal chance of being given the new treatment.  If the trial you are entering into is randomised, it does mean you may not get access to the treatment being tested.


Should you take part in a clinical trial?

There are a number of reasons why you may wish to take part in a clinical trial.  These include:

• Access to new treatments before they become widely available.
   
• Contributing to medical knowledge and the research of cancer.
   
• The potential to be the first to benefit from new methods of treating cancer.
   
• Receiving healthcare provided by leading clinicians in the field of cancer research.
   
• Close monitoring of your health during the trial.
   
• If you wish to do so, discuss the trial with friends, family and your doctor.  It is important that you know that you can leave the trial at any time, without giving a reason.  If, however, you are receiving new treatment as part of the trial, you may not be able to continue to have this treatment if you leave the trial. 

What is informed consent?

Informed consent is a process in which you will receive information, either from your doctor or a dedicated research nurse, before you decide whether or not to take part.  You will be told –

• About the trial, why it is taking place and why you have been asked to take part.
   
• How the trial is going to work (you may or may not get the treatment being trialled).
   
• The standard treatment available if you do not enter the trial.
   
• Information on the treatment options, possible risks/benefits and tests.

You will then arrange to meet with your oncologist at a separate appointment to discuss your choice.  At this appointment you will provide written informed consent if you have opted to participate in the trial.  You may have to undergo blood tests/scans to confirm your eligibility and will then be ‘randomised’ into the trial.  You should only agree to take part in a trial if you are completely happy with what you are being asked to do.


Are there any risks of taking part?

Clinical trials involving patients are the end of a long and careful research process.  Potential risks, however, can include -

• Side effects or risks that are as yet unknown to doctors.
   
• The treatment may be less effective than current approaches.
   
• Benefits to some patients, but it may not work for you.

How do you get involved in a clinical trial?

Some people are offered to take part in a clinical trial by the medical team treating them, whilst others actively seek to enter a clinical trial to potentially get access to treatment that is not currently available in Australia.

Click here to find out more about current clinical and treatment trials being conducted in Australia