Introduction

Many patients receive cytotoxic therapy as an adjuvant (after surgery) or neoadjuvantly (before surgery) so, although you might not be allocated to a specialist chemotherapy day unit, you will meet patients undergoing cytotoxic treatment in many healthcare settings such as wards, the community, hospices and outpatient units. It is essential you understand how these drugs work so you can provide information to help prevent toxicity and ensure prompt identification of any untoward treatment-related symptoms so intervention can be put in place.

Chemotherapy is the use of cytotoxic drugs in the treatment of cancer. It is a systemic treatment which means it travels to all areas in the body (other than the brain due to the blood–brain barrier) through the bloodstream.

Cytotoxic drugs work by disrupting cell division and act on highly proliferating cells more than resting cells. The drug cannot tell which cells are cancerous and which are normal healthy cells, so the drug damages or kills both. However, normal cells have more ability to repair or replace themselves with new cells. This has great significance regarding side effects that patients experience, and knowing which normal cells in the body are affected can assist the healthcare professional prevent, minimise, assess and manage the side effects of cytotoxic therapy.

There are hundreds of cytotoxic drugs, grouped together according to their biochemical nature (Table 10.1). We also classify the drugs in terms of how they act on the cell. Most cytotoxic drugs disrupt the cell cycle by damaging the DNA or affect mitosis and are classified into groups depending on which part of the cell cycle they affect:

Table 10.1 Biochemical classification of cytotoxic drugs

Most cytotoxic drugs are given in combination – usually two or three drugs are used within a regimen. This enhances the effect of the drugs by killing more cells and minimising the range of side effects as well as lessening the risk of cancer cells becoming resistant. For instance, one cell cycle non-specific drug, one cell cycle non-phase-specific and one cell cycle phase-specific drug may be used. Each of the three drugs has different side effects which means the patient is able to tolerate a high dose and a greater tumour kill may be achieved if the drugs all have different modes of action. As an example, the most commonly used chemotherapy regimen for breast cancer after surgery is 5-fluorouracil (5-FU), epirubicin and cyclophosphamide (FEC) (see Fig. 10.1). Sometimes a single drug is used to manage or reduce a patient’s symptoms.

Fig 10.1 Action of FEC cytotoxic drugs on the cell cycle

Cytotoxic drugs and radiotherapy are sometimes given at the same time. This allows for both the primary disease and the secondary spread to be treated. Some cytotoxic drugs act as radiosensitisers, such as paclitaxel, 5-FU and capecitabine. This makes the radiotherapy more effective, however the combination of treatment increases the severity of side effects.

The timing of administration is important. Cytotoxic regimens are given in cycles – most are scheduled and repeated every 21 days over a number of months. This schedule allows normal cells a recovery period before the next cycle is started.

The FEC regimen mentioned earlier involves 6 cycles, each given 21 days apart. Sometimes, a patient’s white blood cell count is reduced and does not return to the normal range at the end of the 21 days – then the next treatment may be delayed or deferred.

Cytotoxic drugs kill a percentage of cells rather than a fixed number, so the first few treatments kill more cells than the last treatment given. This is important if a patient requests to delay treatment. It is important that the early treatments are given to schedule, but there may be leeway with latter treatments (although this may depend on what the aim of treatment is).

Instead of being given in cycles, some cell cycle phase-specific drugs are given continuously. This is achieved by giving the drug orally or intravenously via a central venous access device (CVAD). The advantage of this is that the drug is constantly present in the blood and tissues. When each cell moves into the specific part of the cell cycle, the drug causes damage. Therefore, only a small number of cells are affected at any one time. For example, giving both 5-FU (intravenous) and capecitabine (oral) only damages cells that are in the S phase. A patient receives a continuous dose of 5-FU from a pump via a CVAD. The pump contains 7 days worth of cytotoxic drug and the patient will attend chemotherapy clinic weekly to have the pump changed for up to 6 months. The 5-FU is constant in the blood and tissues and will damage/destroy any cell that enters the S phase. Because only a few cells are being killed, there are fewer side effects.

Preparing the patient for cytotoxic treatment

Like for any treatment, patients must sign a consent form before they receive cytotoxic treatment. It is essential that they understand the reason why the treatment is needed; what is hoped to be achieved; what the potential effects of receiving the specific drugs are; and who they should inform if they experience any adverse side effects.

Before each treatment, the patient’s individual dose is calculated using their body mass index (BMI). Height is measured on the first treatment, but the patient must be weighed at every treatment as they may lose weight, and some may gain weight.

A number of medical tests will also be carried out before treatment is administered. The types of tests undertaken are dependent on the types of drugs used and their toxicities. Blood tests, such as a full blood count, and biochemistry are checked to ensure the patient has normal parameters. Tumour markers (e.g. prostate-specific antigen (PSA) for prostate cancer; Ca125 for ovarian cancer; carcinoembryonic antigen (CEA) for breast, colorectal and lung cancer) are taken as these may be used as a guide to monitor the response to treatment. Depending on the type of toxicity, the following investigations might be performed:

Scans (magnetic resonance imaging (MRI), computed tomography (CT)) may also be done at the beginning, midpoint and at the end of treatment, to judge the response to treatment.

At each cycle of treatment, the patient is reviewed by a healthcare professional to ensure that they are tolerating treatment and the side effects are not too severe.

Routes of administration

Intravenous (IV) is the most common method of giving cytotoxic drugs as it is the most direct way of getting the drug into the bloodstream. However, there is the risk of infection and the procedure is uncomfortable. A variety of intravenous devices are used to access a vein: a peripheral cannula or CVAD such as a skin tunnelled (Hickman) line or Portacath or peripherally inserted central catheter (PICC) line. The choice of intravenous device is dependent on the quality of the patient’s venous access; the length and frequency of treatment; the potential risk of complications from a central venous catheter; the type of drug; and the expected need for additional interventions such as blood transfusions.

Another common method of giving cytotoxic drugs is orally. The number of drugs given this way is increasing due to pharmaceutical developments. It is clearly an attractive method as the patient may receive treatment at home. However, it does result in less contact time from healthcare professionals which may lead to undiagnosed side effects and less psychological support (Irshad & Maisey 2010). There is the issue of concordance (compliance) – patients may not take the tablets as instructed, either forgetting a dose or taking too many. There is also the safety issue of storing medication in the home environment.

Cytotoxics can also be given intrathecally, injected into the spinal canal (via a lumbar puncture) so the drugs reach beyond the blood–brain barrier. This is used to treat patients with leukaemia. This is a potentially hazardous procedure as the risk of infection is high and there is a risk of spinal cord damage. Only three drugs are licensed to be given intrathecally and there have been several fatal cases when the incorrect drug has been given intrathecally instead of intravenously.

Cytotoxic drugs can be inserted directly into a bodily cavity, such as the bladder, pleural and peritoneal cavities. Cytotoxic bladder instillation uses a urinary catheter to insert mitomycin C into the bladder immediately after the surgical removal of bladder cancer. The bladder instillation is repeated intermittently for a number of weeks afterwards. Topical cytotoxic cream can reduce the size of some cancers affecting the skin.

Subcutaneous/intramuscular injections are very occasionally used. However, as most cytotoxic drugs are vesicants or irritants, causing severe tissue damage, and the absorption rate is unpredictable, these routes are not routinely used.