Chemotherapy – What is it?

Chemotherapy is a treatment which uses drugs to treat cancer cells. Sometimes more than one drug is used; this is called combination chemotherapy.

Chemotherapy works on cancer cells in three ways:

1.     It kills cancer cells

2.     It alters the cells damaging potential

3.     It ‘tees up’ the cancer cells for treatment with further drugs (also called pro-drug therapy).

Should I have chemotherapy?

Not a simple response. We said it was complex; each case has to be assessed individually.

To help you decide, ask about the drug’s main side effects and trust in your healthcare team. Be guided by this.

The side effects of chemotherapy depend mainly on which drugs are given and how much. Common side effects include nausea and vomiting, loss of appetite, headache, fever and chills, and weakness. If the drugs lower the levels of healthy blood cells, you’re more likely to get infections, bruise or bleed easily, and feel very weak and tired. You will be checked for low levels of blood cells. Some side effects may be relieved with medicine.

Such is the progress in personalised treatments that neuropathologists can now identify which tumours are likely to respond to chemotherapy. Specific tests might provide information that can be used to influence your treatment and diagnosis. Not all hospitals run such tests but you can ask for them. These tests (also called molecular markers) can:

·         Aid the diagnosis of brain tumours which are sometimes hard to diagnose

·         Allow clinicians to work out a prognosis

·         Indicate whether a tumour will respond to a specific type of treatment

The downside of this is that you may discover that your brain tumour type might not respond to treatment, so if you ask the question, you need to be prepared that you might receive information you’d rather not know.

The MGMT methylation test detects a chemical change in the DNA that shows how the cells are able to fight certain chemotherapy drugs (i.e. repair the damage caused by the drug so that the cancer cells survive and continue to grow).

Tumour samples can also be tested for a ‘1p/19q’ genetic change in the chromosomes that may provide information about the likely sensitivity to DNA acting drugs.

The MGMT and 1p/19q tests will only be relevant to some brain tumours. They can also only be done where a biopsy has been performed, and biopsy material can be obtained and analysed (it does not necessarily matter how long ago the biopsy was performed).

The MGMT methylation test is relevant to all anaplastic gliomas (WHO Grades III and IV).

1p /19q test is relevant to certain tumour types.

The tumour types for which these tests can be done are shown by a tick below.   

Diagnosis Grade MGMT 1p/19q
Anaplastic astrocytoma WHO grade III
Oligodendroglioma WHO grade II
Anaplastic Oligodendroglioma WHO grade III
Oligoastrocytoma WHO grade II
Anaplastic Oligoastrocytoma WHO grade III
Glioblastoma  WHO grade IV

How chemotherapy works

Chemotherapy directly attacks brain tumour cells and disrupts their growth. It is not used to treat all brain tumours and sometimes it is used to shrink a tumour or slow its growth; it won’t always get rid of a tumour. It is generally used to treat a malignant tumour. The blood brain barrier causes problems in the delivery of chemotherapy.The blood brain barrier is there to protect the brain from toxic substances so trying to deliver chemotherapy agents to the site is not easy.

How is chemotherapy given?

Usually in cycles. This gives the patient time for the healthy cells to recover in between treatments. The frequency and length of the treatments depends on the factors mentioned previously. Treatment – rest cycles are often repeated over several months.

What are the major, currently used chemotherapeutic agents?

Main agents used are Procarbazine, CCNU and Vincristine (known as PCV), temozolomide, carboplatin, and carmustine. Until recently, PCV was the mainstay of treatment and temozolomide has been a relatively recent addition. Avastin is the new kid on the block but the jury is still out as to whether this is an effective agent.  Research (2003) has shown that it can cause increased tissue invasion. This treatment may be advised but only in combination with other therapies.

Agent What it is How administered  Side effects
PCV: chemotherapy combination of more than one drug –procarbazine +CCNU (also calledlomustine) +vincristine = PCV. Procarbazine and CCNU are oral medications and vincristine is given intravenously Orally and intravenously over a 28 day cycle Fatigue, nerve discomfort, jaw pain and ringing in your ears.
Temozolomide An alkylating agent that crosses the blood brain barrier and has been approved by NICE. It has shown promise for the long-term management of gliomas and may also be useful inmedulloblastomas and metastatic tumours One to six capsules a few days a month for a year or more. Treatment-rest cycles can last for several months or years.

NB There is little or no difference between PCV and temozolomide apart from the way it is given.

Fatigue, nausea and constipation.
Carmustine A nitrosourea agent which disrupts the DNA of tumour cells to stop them from proliferating. Intravenously or by biodegradable implants (wafers), which are inserted into the cavity left once the braintumour has been removed. The agent is then released directly into the tumour. The wafers dissolve over the next two to three weeks. If administered intravenously, you will be an outpatient and the cycle usually repeats every 6 weeks.

The disadvantage with Carmustine wafers is that the agent does not reach invading cells but remains local.

Wafers may cause seizures, cerebraloedema and problems with wound healing. Side effects include fatigue, nausea and constipation.
Avastin: also called bevacizumab Anti-angiogenic therapy: it inhibits the growth of blood vessels which feed tumour Intravenously. You cannot have Avastin if you are having surgery. This has not been approved by NICE and therefore may not be funded by your commissioning board. Headaches, confusion, vision problems, feeling light-headed, fainting, and seizure

New drugs are being developed and researched. These tend to fall into several camps and would normally be in a clinical trial: 
> Agents that stop cell division

> Anti-angiogenic therapy: these drugs inhibit the growth of blood vessels which feed tumour;

> Differentiating agents: these drugs act on the cancer cells to make them mature into normal cells. They work in three ways:

                                     > They slow down malignancy

                                     > They limit the number of cells dividing

                                     > They sensitise the cells to existing therapies

> Immunotherapy: a seek and destroy mission. These drugs offer a unique method of brain tumour treatment, and are often considered to be separate from chemotherapy. Compared with other forms of cancer treatment such as surgery, radiation therapy, or chemotherapy, immunotherapy is still fairly new. There are different types of immunotherapy. Active immunotherapies stimulate the body’s own immune system to fight the disease. Passive immunotherapies do not rely on the body to attack the disease; instead, they use immune system components (such as antibodies) created outside the body. Immunotherapeutic agents include interferons, natural proteins that are toxic to cancerous cells and specific antibodies. This treatment can improve the immune system’s ability to locate and destroy tumour cells.

> Gene therapy: the transfer of genetic material to a brain tumour cell to destroy the cell or to change the nature of malignant cells so that they become more sensitive to therapy (pro-drug treatment).

> Targeted molecular therapies: these agents block a specific growth pathway which a tumour cell may use (e.g. tk inhibitors).

> Intratumoural therapies: this involves inserting new biological therapies directly into the brain tumour.

How are these agents taken?

> Most commonly by mouth (orally) – some chemotherapy drugs are given in pill or capsule form.

> Injection into a vein (intravenously) – you shouldn’t need to be admitted into hospital for this.

> Injection into an artery (intra-arterially) – not common. This method has fallen out of favour as it has been associated with greater toxicity to the brain.

Information courtesy of brainstrust