Chemotherapy is the treatment of cancer with the use of antineoplastic agents. It aims to attack fast-growing cancer cells in order to slow down or reverse the spread of cancer. It is used in the treatment of most solid tumours and malignancies (such as leukaemia, lymphoma, and myeloma). Chemotherapy has three main goals; to cure certain cancers, control others, and in palliative care to relieve pain or obstruction and improve the sense of well being when no other methods are possible. Chemotherapy can be combined with surgery, radiation therapy, or both depending on the case (Smeltzer, Johnson, & Bare, 2003).
Several factors determine the rate of response of cancer cells to this type of therapy. These include; the mitotic rate of tissue (the faster the rate, the greater is the chance of response), the size of the tumour (the smaller the tumour, the greater the rate of success), the age of the tumour (the younger the tumour, the greater the chance of response), the location of the tumour (since certain sites cannot be reached well with chemotherapy), and the presence of resistant tumour cells (mutation of cells can result in cells resistant to chemotherapy) (Lewis, Heitkemper, Dirksen, O’Brien & Bucher, 2007).
Classification of Chemotherapeutic Drugs
Chemotherapeutic drugs are classified according to their structure and mode of action. Certain drugs (cell cycle specific agents) destroy cells which are actively reproducing. Many drugs are specific to certain phases of the cell cycle. Some interfere with DNA and RNA synthesis, whilst others halt the formation of the mitotic spindle. Cell cycle nonspecific agents on the other hand act independently on the cell cycle phases. Some treatments combine both agents in order to increase the number of tumour cells killed. Classification includes; alkylating agents, nitrosureas, antimetabolites, antitumor antibiotics, mitotic inhibitors, topoisomerase inhibitors, corticosteroids, and platinum drugs (Lewis et al., 2007).
Administration of Chemotherapeutic Drugs
Chemotherapeutic agents can be administered through topical, oral, intravenous, intramuscular, subcutaneous, arterial, intracavitary (pleural, peritoneal), and intrathecal routes. It may also be administered by perfusion or continuous infusion. (Smeltzer et al., 2003) The route depends on the type of agent, the dose, and the type, location, and size of tumour being treated. Many chemotherapeutic drugs can be irritants or vesicants. Irritants damage the intima of the vein, and cause phlebitis and sclerosis and limit future peripheral venous access but do not cause tissue damage if they are infiltrated. Vesicants, however, if accidentally infiltrated into the skin, can cause severe local tissue breakdown and necrosis. Pain is the cardinal symptom of extravasation, but may not always be present. Other signs include swelling, redness, and vesicle presence in the skin. This can potentially progress into a deep wide crater which would then need to be closed by a skin graft (Lewis et al., 2007).
Side Effects and Complications of Chemotherapy
Chemotherapeutic agents cannot distinguish between cancer cells and normal, unaffected cells. Therefore, side-effects result when normal cells are destructed. Cells which are rapidly proliferating, such as those in the bone marrow, the gastrointestinal lining and in the integumentary system are at increased risk of becoming affected. The effects of chemotherapy are caused by general cytoxicity and organ-specific drug toxicities. Response of the body to by-products of cellular destruction may cause fatigue, anorexia, and alterations in taste. General and drug-specific adverse effects are classified as acute, chronic, or delayed (Lewis et al., 2007).
There are a number of gastrointestinal-related side effects, all of which can affect the patient’s nutritional and hydration status as well as the psychological and mental well-being. Nausea and vomiting are very common side effects and can occur within hours of receiving treatment. Oral mucositis (irritation, inflammation, or ulceration of the oral mucosa) and esophagitis (oesophageal inflammation), another form of mucositis are also side effects of chemotherapy. Other side effects include; anorexia, which may develop as a general reaction to treatment; diarrhoea, due to a reaction in the bowel mucosa; and constipation. Toxic effects from chemotherapy may also put the patient at increased risk of developing hepatotoxicity (Lewis et al., 2007).
Bone marrow suppression (myelosuppresion) is one of the most common effects of chemotherapy and may cause complications in red blood cells, white blood cells, and platelets. Anaemia is a decrease in red blood cells or haemoglobin levels and is one such type of myelosuppresion. Patients with anaemia will experience fatigue, which decreases their quality of life substantially. Leukopenia is a low number in white blood cell count and can cause increased morbidity and mortality due to high risk of infection. Thrombocytopenia is characterized by a low number of blood platelets. When platelet count is too low (<20,000/I?l), spontaneous bleeding and major haemorrhage can occur (Lewis et al., 2007).
Since the skin contains rapidly dividing cells, it is very susceptible to chemotherapy effects which may occur throughout the Integumentary system. These include alopecia (destruction of hair follicles), which may lead to hair loss. However, this is usually temporary with chemotherapy. Chemotherapy may also cause skin changes such as photosensitivity, acneiform eruptions, acral erythema (swelling and numbness of hands and feet), hyperpigmentation (darkening of the skin), and telangiectasis (dilatation of capillaries near skin surface) (Lewis et al., 2007).
Side effects associated with the genitourinary systems include; haemorrhagic cystitis, when cells which line the bladder are destroyed; reproductive dysfunction; and nephrotoxicity due to damage in renal cells (Lewis et al., 2007).
Peripheral neuropathy is a possible side effect of chemotherapy, particularly plant alkaloids and cisplatin, and may cause paresthesias (abnormal skin sensations), areflexia (absence of reflex), skeletal muscle weakness, and smooth muscle dysfunction (Lewis et al., 2007).
Chemotherapy has the potential to cause progressive and irreversible pulmonary toxicity and tissue damage. Pulmonary toxicities include noncardiogenic pulmonary oedema, hypersensitivity pneumonitis, interstitial fibrosis, and pneumonitis due to inflammation (Lewis et al., 2007).
Pericarditis and myocarditis can be the side effects of some chemotherapeutic drugs. Cardiotoxicity is another serious side effect, which causes ECG changes and rapidly progressing heart failure and left ventricular dysfunctions (Lewis et al., 2007).
Biochemical Side Effects
Hyperuricemia, an abnormally high level of uric acid in the blood, can be caused by chemotherapy- induced cell destruction. In long term, this can lead to secondary gout and obstructive uropathy (Lewis et al., 2007).
Psychoemotional Side Effects
Fatigue is one of the most common side effects of chemotherapy. This is due to an accumulation of metabolites from cell breakdown. It is nearly a universal symptom affecting up to 100% of oncologic patients (Lewis et al., 2007).
Chemotherapy-Induced Nausea and Vomiting
Chemotherapy- induced nausea and vomiting (CINV) are two of the most distressing side effects of chemotherapy, with patients ranking nausea as their first and vomiting as their fourth most feared symptoms (DiVall & Cersosimo, 2007; Miller & Kearney, 2004). CINV is associated with a rise in clinical complications, such as dehydration and poor nutrition, and a decrease in the overall quality of life, making it difficult for the patient to perform activities of daily living (Hawkins & Grunberg, 2009). Poorly managed CINV is also related to increased length of stay and costs, and may even result in the refusal of beneficial treatment. Prevalence is estimated between 60% and 72% and varies according to cancer and treatment modalities (Miller & Kearney, 2004; Hawkins & Grunberg, 2009; Schnell, 2003). Nausea is defined as “an unpleasant feeling in the back of the throat and stomach that may or may not result in vomiting”, whilst vomiting is “a forceful contraction of the abdominal muscles to cause stomach contents to come up through the mouth” (Tipton, McDaniel, Barbour, Johnston, Kayne, et al., 2007).
Pathophysiology and Risk Factors
Acute nausea occurs within a few minutes to several hours after administration and often resolves within 24 hours. Delayed nausea occurs after 24 hours post-administration and can last up to 7 days (Tipton et al., 2007). Anticipatory nausea occurs before patients receive treatment and is a conditioned response mostly due to past negative experiences with chemotherapy. It may be triggered by anxiety, odours, or tastes. Breakthrough CINV occurs in spite of preventive treatment and requires rescue medication. Nausea and vomiting can be divided into; nausea, retching, and vomiting. Retching and vomiting are thought to be brainstem responses whilst nausea involves higher brain regions and is not well understood. Nausea is subjective and may be accompanied by pallor, salivation, tachycardia, and diaphoresis. Retching involves the rhythmic contractions of the diaphragm, abdominal, and chest muscles, and precedes vomiting. The latter involves a reflex arc where signals are sent to the dorsal vagal complex and these activate somatic and visceral impulses to abdominal muscles, oesophagus, stomach, and diaphragm (Hawkins & Grunberg, 2009).
Females are thought to be at a higher risk of developing CINV, as are those between ages 6 and 50 years. Prior history of morning and motion sickness, and high levels of anxiety all correlate with an increased risk as are those with previously poorly controlled nausea and vomiting. The incidence is also determined by the emetogenic potential of the given chemotherapy agent, with cisplatin being one of the most highly emetogenic agents (Hawkins & Grunberg, 2009; Schnell, 2003).
Assessment for CINV is an ongoing process that should begin with initial patient contact and continues throughout successive chemotherapy cycles (Bender, McDaniel, Murphy-Ende, Pickett, Rittenberg, et al., 2002). A systemic approach is essential and the primary goal should always be that of prevention. Patient assessment is an oncology nurse’s responsibility and each patient should be assessed for risks individually (Miller & Kearney, 2004; Hawkins & Grunberg, 2009). During initial contact, the patient should be assessed for a prior history of nausea and vomiting and their risk factors. Information about the patient’s past health history, including illnesses, operations, and pregnancies may provide guidance. Patients should be asked to bring in their medications and asked about their expectations regarding symptoms associated with treatment. The nutritional status (including weight and height), laboratory work, physical exam, and diet history should also be assessed and the chemotherapy regimen should be reviewed for its emetogenic potential. The latter is the most crucial factor in determining the expected levels of nausea and vomiting (Bender et al., 2002; Hawkins & Grunberg, 2009). One should also consider the drug dose, route, and frequency in relation to the risk of patient developing CINV.
Many instruments may be used to assess CINV. Instruments that can be completed and reviewed quickly decrease patient and family burdens as well as nursing time. Additionally, self-report instruments are preferred over observation because of the subjective nature of CINV. Some instruments used to assess CINV include “The Symptom Distress Scale” and “The Memorial Symptom Assessment Scale”. Scales that measure only nausea and vomiting include; “The Index of Nausea, Vomiting, and Retching” and visual analogue scales. Nurses should evaluate the effectiveness of interventions by recording the time of onset and duration of nausea and vomiting and proper documentation is critical for future management. The use of any non pharmacological interventions (including herbal preparations) and their effectiveness should be noted. Finally, cultural sensitivity should be kept in mind when assessing symptoms of CINV (Bender et al., 2002; Miller & Kearney, 2004).
The patient’s quality of life can be significantly improved by the administration of the appropriate antiemetic therapy, be it by pharmacological or behavioural means. The best management strategy should be based on the individual, taking into consideration the prescribed chemotherapy regimen, convenience, and cost-effectiveness. One should always keep in mind that the primary goal is to prevent, rather than treat, CINV (Miller & Kearney, 2004).
There are currently three classes of approved anti-emetic agents which, according to the ASCO (American Society of Clinical Oncology), have the highest therapeutic index; the 5-HT3-receptor antagonists, the corticosteroids, and the NK1-receptor antagonists. There are four available agents of the 5-HT3-receptor antagonists; dolasetron, granisetron, ondansetron, and palonosetron. These work by blocking serotonin receptors in the brain stem and hence inhibit serotonin release in the GI tract. Corticosteroids can be used as single agents or in combination to prevent both acute and delayed CINV. Dexamethasone is effective in patients receiving drugs with low emetogenic potential. When used in combination with 5-HT3-receptor antagonists and/or aprepitant, dexamethasone efficacy is increased and hence can be used for prevention of CINV caused by highly emetogenic chemotherapy. Neurokinin-1-receptor antagonists, such as aprepitant, act by blocking the binding of tachykinin substance P to neurokinin receptors in the gut and emetic centre in the brain stem. Other antiemetic agents such as phenothiazines, metoclopramide, and cannabinoids have a greater risk of toxicity and lower efficacy but can also be used in treatment of CINV with close supervision (DiVall & Cersosimo, 2007).
In 2007, Vrabel reviewed six studies which compare the efficacy of ondansetron and granisetron. It was concluded that both are equally good choices in the management of CINV, and although new drugs such as dolasetron and palonosetron are available, older drugs such as aprepitant and 5-HT3-receptor antagonists provide effective antiemetic coverage, are less expensive, and are more likely to be covered by the patient’s insurance. Schnell (2003), states that comparative trials with high dose metoclopramide show that dolasetron, ondansetron, and granisetron are more effective in the prevention of acute CINV and are better tolerated and preferred by most patients. 5-HT3-receptor antagonists are the agents of choice in preventing acute CINV after moderate or highly emetogenic chemotherapy.
Non-pharmacological interventions should not replace standard therapy, but used in conjunction with the aim to increase the patient’s quality of life. Such interventions have the advantage that they can be easily administered and learned within the chemotherapy environment and have few, if any, side effects. Progressive muscle relaxation training (PMRT), guided imagery, self hypnosis, cognitive distraction (such as computer games), and music therapy (low frequency and slow rhythm) are some interventions which may be useful (Miller & Kearney, 2004). Richardson, Smith, McCall, Richardson, Pilkington, et al. (2007), add that hypnosis can be used as an approach to experience changes in sensation, perception, and behaviour, whilst enhancing relaxation. Meta-analysis demonstrated that this intervention can be clinically valuable for anticipatory CINV, especially in children; however, further studies still need to be conducted.
Acupressure is a non-invasive procedure where pressure is applied by the thumbs, fingers, and hands on the skin surface at key points. It is a type of Chinese medicine the goal of which is to restore the body to a state of energy balance. It can be administered by the healthcare providers, family, or patients themselves and does not involve skin puncture. For the treatment of nausea, digital pressure should be applied at point P6, located on both forearms, and using the thumb of the opposite hand and held for a maximum of three minutes (Dibble, Luce, Cooper, Israel, Cohen, et al., 2007).
Inadequately managed CINV can result in a number of consequences such as impaired nutritional intake which may lead to anorexia, weight loss, muscle wasting and fatigue; electrolyte imbalances, leading to dehydration, renal toxicity, aspiration pneumonia, and oesophageal damage. The nurse should therefore encourage the patient to maintain a food diary, and assess for signs and symptoms of electrolyte imbalance. Accurate records of fluid loss should be assessed and abnormal laboratory values reported. The patient should also be assessed for signs and symptoms of pneumonia resulting from aspiration of vomitus. Over-sedation during chemotherapy should be avoided and vomiting prevented by proper drug administration. Patients may experience behavioural consequences as a result of uncontrolled CINV, which may also include sexual dysfunction and relationship burdens (Bender et al., 2002).
Guidelines and Implications
The National Comprehensive Cancer Network (NCCN) came up with a number of guidelines to help manage CINV. These guidelines recommend that patients should be given a 5-HT3 antagonist every day before chemotherapy is started as well as dexamethasone. Dexamethasone should be given for two to three days following chemotherapy. If highly emetogenic chemotherapy is administered, aprepitant is also suggested, at a dose of 125mg followed by 80mg on the second and third days. Breakthrough emesis is more difficult to control and guidelines recommend treatment by additional agents from a different class. The NCCN states that the main goals should be to prevent CINV, obtain control in all settings, that treatment should have no side effects and be convenient and easy to use, and that the cost should not be a barrier (NCCN, 2004).
Antiemetics should be administered 30 minutes prior to chemotherapy (except for aprepitant, which should be administered 1 hour before chemotherapy), and continued for as long as chemotherapy is administered. Patients should be given as needed antiemetics for breakthrough CINV using an agent from a different class of drugs (DiVall & Cersosimo, 2007).
Only pharmacologic interventions are supported by strong evidence for effectiveness and are recommended for practice. Additional research on non-pharmacologic interventions needs to be conducted. Oncology nursing staff must be educated about evidence-based interventions and their ability to learn, teach, and perform should be assessed (Tipton et al., 2007) (See Appendix A). Despite the fact that implementing guidelines result in better patient outcomes, oncology nurses often do not adhere to such guidelines, particularly when it comes to prophylaxis of delayed CINV since symptoms appear after the patient leaves the treatment centre (Hawkins & Grunberg, 2009).
A lot of progress has been made in understanding the pathophysiology, pharmacological and behavioural management of CINV and the introduction of potent antiemetics has significantly improved the patient’s quality of life and compliance with chemotherapy regimens. Effective prophylaxis should begin with the first chemotherapy regiment and both acute and delayed CINV need to be addressed (Bender et al., 2002; DiVall & Cersosimo, 2007). Also, evidence-based guidelines are essential and should be established in oncology settings and institutions by oncology nurses. More accurate assessment and communication with patients can improve adherence, and more time is needed to address queries, account for differences in education, language, cultural background, and expectations (Hawkins & Grunberg, 2009). Effective control during the patient’s initial treatment retains their quality of life and positive attitude towards chemotherapy. In addition, pharmaco-economic benefits are attained resulting in a decrease in hospital stays, and hence, lower hospital costs and resource consumption (Schnell, 2003). In spite of all this, more research still has to be carried out to identify pharmacologic agents, and more investigations are needed to test the effectiveness of behavioural and non-pharmacological strategies to manage CINV (Bender et al., 2002).