2   What does T4, N1, M1 (Stage IV) mean in terms of George’s cancer?

3   Why is George having cytotoxic chemotherapy?

4   How do cisplatin and vinorelbine work?

5   Why is it better to give George a combination of drugs in his cytotoxic chemotherapy?

6   What is the role of the nurse in monitoring and managing the potential side-effects of George’s medicines?

7   How would using aprepitant, ondansetron and dexamethasone help in preventing and controlling George’s nausea and vomiting?

ANSWERS

1 Why does George have dyspnoea on exertion and a cough?

As the cancer cells accumulate, tumours form which may press on other structures to produce symptoms. George, for example, has squamous non-small-cell lung carcinoma (NSCLC) which has formed a tumour occupying his left upper lobe. This has reduced the flow of air in and out of his left lung, leading to breathlessness on exertion. It has also caused a local inflammation which has generated sputum production, hence the cough (Merkle and Loescher 2005; King and Robins 2006).

2 What does T4, N1, M1 (Stage IV) mean in terms of George’s cancer?

A Investigations help to determine the stage of the cancer which in turn influences the type of treatment. George’s NSCLC was staged at T4, N1, M1 (Stage IV) using the American Joint Committee on Cancer (AJCC) TNM staging system. In this system, a combination of letters and numbers communicate information about the tumour (T), presence and location of lymph nodes (N) and the absence or presence of metastases (M). T1, for example, represents a tumour which is confined to the organ of origin compared to T4 which indicates that the cancer has invaded other structures and solid organs. Lymph node status ranges from 1 to 3 with increasing involvement of regional lymph nodes. Metastases is represented by 0 or 1, in other words, there is (1) or is not (0) evidence of metastases. A zero score next to T, N or M indicates that there is no evidence of a tumour, lymph node involvement or metastases (Yarbro et al. 2011).

TNM has different meanings for different tumours and can be found in the TNM atlas (Rubin and Hansen 2008), however the T4, N1, M1 staging of George’s NSCLC indicates that his tumour was at the most advanced of the T stages due to extension into the pulmonary artery and that there was evidence of lymph node involvement (N1) and metastases (M1). Once the TNM staging has been completed, this information is used to give the cancer an overall stage, which in George’s case is Stage IV. Cancers are normally staged between I and IV, with I representing early stage cancer and IV representing the most advanced. The stage of a cancer is used to assess prognosis and inform the choice of treatment (Gabriel 2004).

3 Why is George having cytotoxic chemotherapy?

A Cytotoxic chemotherapy is a form of treatment which causes cell death, predominantly targeting cells (both normal and cancer) which are in the process of dividing. The treatment interferes with the cells’ ability to reproduce. The aim is to maximize damage to the cancer cells while minimizing harm to normal cells.

Cancer cells go through the same phases of the cell cycle (Barber and Robertson 2012) as normal cells and many cancer drugs act by blocking one or more of these phases. Cytotoxic drugs can be classified as cell cycle non-specific or cell cycle specific (Brenner and Stevens 2006). Those which are cell cycle non-specific are effective in damaging cells which are both resting and dividing. Cell cycle specific drugs only damage cells which are in a particular phase of cell reproduction (Barton-Burke and Wilkes 2006).

A CISPLATIN

Cisplatin is a platinating agent which is used for the treatment of lung cancer (BNF 2012). It is a cell cycle non-specific drug which works both in a number of phases of the cell cycle and also in the resting phase (G0). It has a similar action to alkylating agents which damage and impede the replication of DNA (Rang et al. 2012). Other cell cycle non-specific drugs include antibiotic agents such as bleomycin and epirubicin which also damage DNA. Cell cycle specific drugs include antimetabolites such as methotrexate and mitotic poisons such as vinorelbine. The antimetabolites interfere with DNA replication and tend to be most effective in the S or M phases. The mitotic poisons prevent the formation of mitotic spindles which are essential for cell division in mitosis (Galbraith et al. 2007).

VINORELBINE

Vinorelbine acts in the M phase of the cell cycle by binding to the spindles of the cells, preventing separation of the chromosomes and thus inhibiting mitosis (Simonsen et al. 2006; Chen and Moore 2007).

5 Why is it better to give George a combination of drugs in his cytotoxic chemotherapy?

A Cancers which have a greater proportion of cells in the cell cycle (are dividing), and are growing quickly, are likely to respond better to cytotoxic chemotherapy than those dividing less frequently. As cells will all be at different phases of the cell cycle, at any one time, drugs tend to be given in combination to increase the likelihood of killing as many cells as possible. Cisplatin, for example, is most effective in the G0, G1 and S phases, whereas vinorelbine works best in the M phase. Giving combinations of cytotoxic chemotherapy drugs is therefore more effective than giving single agents alone. Unfortunately, cytotoxic chemotherapy targets not only cancer cells, but any cell which is in the process of dividing. As treatment primarily affects cells which are in the process of reproduction, normal cells which reproduce frequently tend to be affected most. These include epithelial cells such as hair and those which line the digestive system, blood cells formed in the bone marrow and the ova and sperm of the reproductive organs (Rang et al. 2012).

6 What is the role of the nurse in monitoring and managing the potential side-effects of George’s medicines?

A The role of the nurse is varied, and involves monitoring and managing the following aspects of care.

•   As both cisplatin and vinorelbine can cause myelosuppression, patients are at risk of infections, anaemia and bleeding. A full blood count should be undertaken prior to each cycle of treatment and the patient should be advised that treatment will be delayed if they are neutropenic (neutrophil count less than 1000 cells/mm³). Patients should be monitored carefully for evidence of infection and/or fever and should be advised to protect themselves from infection – for example, by avoiding exposure to people with known infections (Lilley 2006). They should also be advised how to recognize early signs of infection, including monitoring of their temperature. Patients should be asked to take their temperature prior to analgesic medication which may mask infection through its antipyretic activity, and seek immediate medical advice if they have a pyrexia greater than 37.5°C in case anti-biotic treatment is needed. Patients may also become anaemic leading to shortness of breath, dizziness or fatigue, and low platelets may lead to unexplained bruising or bleeding. Patients should be advised how to recognize such symptoms and urged to report them promptly.

•   Certain side-effects cannot be prevented, however, patients should be advised to report any hearing loss, buzzing in the ears, pins and needles or altered sensations in fingers or toes. The latter may result in patients being unable to feel extremes of temperature so they should be advised to take care with very hot or cold objects. Assessment of sensory and motor function is therefore important as treatment may need to be stopped if symptoms are severe. Hair may become thinner, though complete hair loss is not usual. Patients may be referred for a wig if desired.

7 How would using aprepitant, ondansetron and dexamethasone help in preventing and controlling George’s nausea and vomiting?

A Patients at high risk of nausea and vomiting due to cytotoxic drugs should be prescribed a 5-HT₃-receptor antagonist in combination with dexamethasone and aprepitant. The 5-HT₃ antagonists such as ondansetron block the action of serotonin in the nucleus tractus solitarius and chemoreceptor trigger zone by binding to the 5-HT₃ receptors and blocking transmission of impulses to the vomiting centre. Aprepitant is used to prevent nausea and vomiting by inhibiting the action of substance P in the emetic pathways and dexamethasone in combination with other drugs such as ondansetron is highly effective, though the exact mechanism is unknown (Perwitasari et al. 2011).

As cisplatin is highly emetogenic, anti-nausea treatment is prescribed prior to the administration of chemotherapy in an attempt to prevent the experience of nausea and vomiting. It can also be used to ameliorate symptoms should they occur. It is important to achieve good control during the first cycle of chemotherapy in order to avoid anticipatory nausea and vomiting, though the emetogenic potential of cisplatin may be too powerful to eliminate. Although current emetogenic treatments are 70–80% effective in preventing and treating nausea and vomiting in patients receiving cytotoxic chemotherapy with high emetogenic potential, there are still patients who experience this distressing symptom.