Keywords

Introduction

The number of patients affected by chronic diseases, including cancer, continues to grow. Over the past two decades, the median age at diagnosis of cancer has increased around 70 years of age, as a result of a generally better life expectancy. Healthcare services will have to adapt to the increased number of cancer patients presenting with age-related comorbidities and chronic disease. The development of many oral agents, mostly targeted therapy, is shifting the cancer care point of care from the hospital, where chemotherapy and invasive treatments are administered, to an ambulatory setting and ultimately to home care. In contrast to chemotherapy that has a broad and relatively non-specific spectrum of cytotoxicity, targeted therapies specifically block or enhance a specific intracellular pathway involved in the development and promotion of a specific tumour type. Targeted therapies rarely eradicate cancer but rather switch them to a more chronic state, delaying the progression and ultimately extending overall survival. This implies that targeted therapies are taken chronically for often an extended period of time. Because they target specific physiological pathways, usually redundant in cancer and normal cells, targeted therapies are very specific and have varied side effect profile. It is therefore essential to provide a support system for the patient and his specific therapeutic environment that responds to this major change. In addition to their anticancer treatment, many patients are also receiving multiple medications for other diseases, with multiple drug interactions, ranging from reducing the anticancer agent activity to critically increasing toxicity causing severe side effects or even death of the patient. Hence, health professionals have to pay particular attention to the co-medications. Another critical conundrum of oral agents is the compliance/adherence issue. When prescribing injectable agents, physicians control precisely the dose and administration schedule. In case they prescribe oral drugs, they rely on the patient adherence and compliance to achieve a correct therapeutic target.

According to the World Health Organization (WHO 2003 report), the proportion of patients affected by chronic disease that complies with their treatment is only about 50% [1]. Health professionals have in the past believed that adherence to treatment of cancer patients was better than most patients with chronic disease because of the fear of the recurrence or the death. Contrary to these beliefs, different studies have shown that this compliance is far from being optimal [2]. Noteworthy, the patient is not only the source of compliance’s issue, the role of providers being also important. A system approach of compliance and adherence is therefore required. According to the WHO report, a single-factor approach might be expected to have limited effectiveness. The most effective approaches have been shown to be a multilevel – targeting more than one factor with more than one intervention (e.g. education in self-management; pharmacy management programmes; nurse, pharmacist, and other non-medical health professional intervention protocols; counselling; behavioural interventions; and follow-up and reminders, among others). Several programmes have demonstrated good results using multilevel team approaches, involving multidisciplinary and multi-professional models. The WHO recommends applying therapeutic education, a support helping the patients to become autonomous (to be empowered), to take care of themselves in order to maintain or improve their quality of life, their well-being. Education is a main part of nurse’s support role of patients taking oral treatments. Education of patients receiving anticancer oral treatment aims at their empowerment to secure their journey, to improve the efficiency of the treatment, and to preserve their quality of life. Transversal and multi-professional care pathways, involving physicians, nurses, pharmacists, dietitians, psychologists, other related healthcare professionals, and properly educated patients, will secure an efficient delivery of the medication.

General Measures

Before prescribing oral drugs and initiating treatment, the following general measures should be considered by healthcare professionals. According to Goodin et al., they should provide patients and caregivers with education and training to understand how to take treatment safely. Patient documentation and other educational materials should be continuously evaluated to ensure accurate and up-to-date information. The patient’s consent for oral anticancer treatment should be obtained. The ability of patients to take oral treatment and to comply with their treatment plan should be evaluated. Patients should also be informed of all issues related to safe handling. The drug interactions of the usual treatment should be examined. Interference with diet and clear instructions on dosage should be provided, including what to do when a dose is missed or when vomiting occurs. During prescription referrals, any potential drug and food interactions should be reassessed and discussed with the patient or caregiver. The patient should be made aware of the required surveillance arrangements by having access to the written protocol and treatment plan of the facility where treatment was initiated [3].

The main side effects that can significantly impact the patient’s health and quality of life, especially in the case of new targeted agents that are sometimes prescribed continuously over long periods of time, must be known by the physician and the patient. The identification of the main classes of drugs, the exhaustive knowledge of their side effects, proper monitoring, and in-depth education of nurses and patients are key elements to secure the efficacy of these therapies.

Main Side Effects of Targeted Therapies and Their Management

We have summarised the most frequent side effects within four main groups: dermatological, cardiovascular, oral and upper gastrointestinal, and metabolic toxicity, including fatigue. The most commonly used classification is the Common Terminology Criteria for Adverse Events (CTCAE) [4].

Dermatological Side Effects (Table 4.1)

Many targeted therapy drugs cause skin reactions. They usually develop slowly after a few days or weeks and can range from mild (minimal skin changes or Grade 1) to severe (painful ulcerative dermatitis or Grade 3). They are not signs of a drug allergy, which often includes other serious symptoms such as difficulty breathing, dizziness, tightness in the throat or chest, or swelling of the lips or tongue.

Table 4.1 General prophylactic measures to keep the patient skin in a good condition [5]
Full size table

Patients have to be informed about the skin symptoms that might occur during the course of their treatments before they have started the treatment to help prevent skin changes or at least try to keep them under control. Preventive as well as symptomatic measures have to be advised to optimise quality of life and improve treatment compliance. It is essential to identify whether the skin symptom is related to antineoplastic therapy or not. Cancer patients are often presenting with inflammatory, infectious, and specific skin lesions as well as graft-versus-host disease-related rash. They regularly also take multiple drugs, and it is not easy to know which one is responsible for the skin condition. Another critical point is to evaluate the serious skin reactions that require treatment discontinuation and/or specific management.

Skin changes frequently occur as a result of the targeted agent mode of action, the skin being a very sophisticated environment controlled by regulatory pathways largely similar to the cancer pathways. Drugs such as EGFR inhibitors (e.g. cetuximab (Erbitux®), panitumumab (Vectibix®), erlotinib (Tarceva®)) target the epidermal growth factor receptor (EGFR) protein, which tells the cancer cells to grow and divide. The normal skin’s homoeostasis heavily relies on the EGFR pathway, so that drugs targeting the EGFR pathway can switch off the signal for skin cells to grow normally and make it harder for them to retain moisture, leading to dry skin.

Dry skin (xerosis) can start within the first few weeks after the first intake of the targeted therapy drugs and is reported in about one third of the patients after 1–3 months. It is observed in almost all the patients treated with EGFR inhibitors. But nearly everyone getting targeted therapy has dry skin after 6 months of treatment. The skin can become dry, itchy, scaly, and brittle and may even crack open. Hands and feet are especially concerned [6]. Dry skin is best controlled by using emollients applied on humid skin to be more effective.

Fissured dermatitis of the finger pulp or heels can be treated with vitamin A- or urea-based ointments.

Prophylactic Measures for Dry Skin

To keep the skin in a good condition, it is essential:

  • To moisturise the skin at least twice a day with an unscented greasy cream

  • To use mild shower/bath oils, moisturising and preferably unperfumed without alcohol because of its drying effect

  • To apply cream on the skin as clean as possible, especially after washing, showering, or bathing

Rash (Papulopustular Rash/Folliculitis of the Seborrheic Areas)

It usually appears during the first week of treatment at various degrees and is often described as acneiform while differing from acne in the absence of retentional lesions or presence of comedones. In most people, the rash is mild, but nevertheless profuse eruption may occur, and it is described as uncomfortable and sometimes painful [7, 8]. It is worth informing the patient that the occurrence and intensity of this eruption is associated with a better tumour response and overall survival. The hypothesis is that some polymorphisms of EGFR might be associated with the appearance of cutaneous signs and a better antitumor response. Another hypothesis is a better bioavailability of the drug in the skin and the tumour as well as a beneficial effect of the inflammatory/immune reaction in the skin and perhaps also in the tumour [9]. These authors also pinpoint the importance to differentiate moderate rash from serious hypersensitivity reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome or Stevens-Johnson syndrome usually associated with mucosal involvement, bullous lesions, and systemic and biological signs.

Management of Rash

  • Mild skin changes (Grade 1) may not need treatment. They include rashes that are only in a limited area, that are not causing any distress, and that are not infected. Moisturising creams or ointments that contain no alcohol, perfume, or dye can sometimes help with dryness. Other, more symptomatic lesions need topical treatment relying on local antibiotics (erythromycin, clindamycin, metronidazole) and copper- and zinc-based antiseptic creams. When antibiotics are not sufficient, topical corticosteroids are usually effective. Camouflaging the lesions with appropriate non-comedogenic makeup (water-based) is allowed.

  • Moderate skin changes (Grades 2–3) include a rash over a larger area of the body or skin changes causing mild distress from itching or soreness, but with no signs of infection. It will be advised to watch closely to see if the rash gets better or worse. Systematic treatment such as cyclins (doxycycline, 100–200 mg/day) is used at first-line therapy for 4–8 weeks longer if needed. The dose of the targeted therapy drug usually does not need to be changed for moderate skin problems.

  • Severe skin changes (Grade 3) are bad rashes that cover a lot of skin, cause itching and soreness affecting the quality of life (such as sleep problems or pain), and are likely to get infected. A dose reduction is advised if the treatment is poorly tolerated by the patient. If the rash doesn’t get better within about 2 weeks, the targeted drug is often stopped until the skin changes improve. The symptoms rapidly attenuate after reduction or interruption of treatment and do not always recur upon resumption of the drug. The treatment may then be restarted with continued skin care. Treatment is much more likely used for moderate changes, including creams or gels, as well as systematic oral antibiotic. Along with this, a course of corticosteroid pills is often given [10].

Prophylactic Measures

Antibiotics might reduce the relative risk of severe rash associated with EGFR-targeted agents by 42–77%. Vitamin K cream is also identified as having a potential role in the management of EGFR-targeted agent-induced rash [11].

The hand-foot syndrome (HFSR) is a typical feature of angiogenesis inhibitors targeting the vascular endothelial growth factor (VEGF) axis, including, for example, the anti-VEGF bevacizumab (Avastin®), tyrosine kinase inhibitor sorafenib (Nexavar®), sunitinib (Sutent ®), pazopanib (Votrient®), and axitinib (Inlyta®). VEGF helps the tumour to build and keep a blood supply, but they also seem to be important to the very small blood vessels in the hands and feet. Blocking these proteins leads to damage in these tiny blood vessels with the drugs leaking out damage and causing the hand-foot syndrome.

The earliest symptoms of HFSR are sensitivity, tingling, numbness, and pain in the hands and feet. The palms of the hands and the soles of the feet become red. In some cases, the redness looks like sunburn with blisters. The blisters can open up and become sore in severe cases. The lesions are located on pressure or friction areas, they can rapidly become hyperkeratotic, and this phenomenon is often bilateral and symmetrical. HFSR can be very painful. This side effect can affect the ability to walk and to do normal activities [12].

Management of HFSR [13]

  • Mild (Grade 1) HFSR can be controlled by simple symptomatic measures including moisturising creams, keratolytic agents such as 40% urea, and/or creams or ointments containing 1–10% salicylic acid on the calloused areas.

  • Grade 2 HFSR. In addition to the symptomatic measures recommended for Grade 1 HFSR, topical corticosteroids (clobetasol) can be initiated for a few days on inflammatory lesions. If needed, analgesic treatment should be prescribed. In some cases, a dose reduction of 50% should be considered.

  • Grade 3 HFSR. Symptomatic measures should be prescribed as well as antiseptic treatment of blisters and erosions. Treatment should be interrupted for a minimum of 7 days and until toxicity has resolved to Grades 0–1. The resumption of treatment should be begun at a reduced dose for a minimum of 7 days. After a second or third occurrence of Grade 2 or Grade 3, resumption or dose re-escalation should be based on clinical judgement and patient preference. No systematic therapy is recommended.

Preventive measures include removal of pre-existing areas of hyperkeratosis calluses by mechanical or chemical keratolytic treatment (topical 10–50% urea, 2–5% salicylic acid ointments). The patient should be advised to wear comfortable and flexible shoes with padded or gel- or foam-based shock absorber insoles, avoid friction and trauma arising from exercise, and reduce exposure of the hands and the feet to hot water. They should treat dryness and cracking areas with emollients, moisturising creams, or ointments.

Paronychia is the appearance of red and sore cuticles, the areas around the nails. Paronychia is less frequently observed than rash and occurs after at least a month of treatment. It can look like an inflammation of the periungual folds or resemble an ingrown nail. It more often affects the large toes than the fingers (thumbs). Swollen, red, and painful sores can appear around the fingernails and toenails. These sores may become infected and can affect the ability to walk. Nails may also become brittle and grow more slowly [14].

Management of paronychia is aimed at reducing the extent of the granulation tissue using either topical corticosteroids, chemical cautery with liquid nitrogen (silver nitrate or trichloroacetic acid), or even surgical excision followed by the application of phenol.

Prophylactic measures include advising patients to avoid too much pressure on the shoes when jogging, walking, jumping, etc. They have to be informed to avoid friction-traumas-manipulations and to wear wide, open shoes.

Changes in Hair or Skin Colour

Targeted therapy-related hair modifications are underreported in the literature. Some targeted drugs can turn the skin or hair in a yellowish colour during treatment (e.g. with pazopanib (Votrient®) and sunitinib (Sutent®)). For a few people, the hair and/or skin gets darker. This tends to go away once treatment ends. Almost all the patients treated with kinase inhibitors or blocking antibody drugs have a change in hair texture (e.g. the hair on the head becomes thin, dry, straw-like and brittle, or even curly) after 2–3 months. Long-term use may lead to bald patches or alopecia (with sorafenib slightly less with sunitinib and pazopanib). Sores on the scalp and on other hairy areas can appear. Scars caused by these sores may keep hair from growing back after treatment. Facial hypertrichosis for both men and women may grow faster than usual, including longer, thicker, and curly eyebrows and eyelashes. But in some men, facial hair growth slows down. Eyebrows may thin out as well. These changes may usually be noticed later on a course of treatment [15].

Prophylactic Measures

Advise patients to use hair conditioners, to wax their facial hair, and to regularly trim their eyelashes to prevent conjunctiva and keratitis. Patients with trichomegaly who complain about symptoms of eye irritation should be seen by an ophthalmologist, because other ocular conditions such as conjunctivitis and keratoconjunctivitis sicca can complicate anti-EGFR therapy (e.g. erlotinib (Tarceva®)). Trimming and epilation have been found to be satisfactory, safe therapeutic options [16]. It would be the role of the nurse to suggest a list of recommended wigmakers.

Oedema may occur in the periorbital areas in the morning and inferior parts of the body in the evening. They appear very frequently on an average of 6 weeks after initiation of anti-kit, platelet-derived growth factor receptor (PDGFR) treatment (e.g. imatinib (Gleevec®)) [17]. The eyes may burn and become red or dry. In some people, the eyelids get red, tender, and swollen, and the lashes may become crusty. Sometimes the eyelids may turn inwards or outwards. Distorted eyelids or prolonged dryness can damage the cornea.

Management of Oedema

Moderate periorbital oedema does not require any treatment. Severe and/or diffuse oedema can be alleviated by diuretics and electrolyte monitoring. If the eyelids are crusty or swollen, careful cleansing and clean, warm, wet clothes laid over closed eyes may help.

Cardiovascular Side Effects

Most targeted therapies and combination treatment are associated with an increased risk of cardiovascular toxicity [18].

Cardiomyopathy and Left Ventricular Dysfunction

Targeted therapy (type II agents) such as trastuzumab (Herceptin®) and the tyrosine kinase inhibitors sunitinib (Sutent®), lapatinib (Tyverb®), and imatinib (Glivec®) have shown to induce cardiomyopathy. However, in contrast to type I agents, which include chemotherapy like anthracycline, mitoxantrone, or cyclophosphamide, that induce irreversible myocardial damage, type II agent cardiomyopathy is potentially reversible [19].

Coronary Artery Disease

Antiangiogenic drugs have been shown to induce coronary events mainly via two different mechanisms: coronary artery vasospasm and arterial thrombotic events by inhibition of the vascular endothelial growth factor (VEGF).

Cardiac Arrhythmia

Most arrhythmias are not clinically significant. The most concerning is the prolongation of the QT/QTc interval with the associated increased risk of torsade de pointes. This is common among patients treated with multi-targeted kinase inhibitors and angiogenesis inhibitors. Early detection by regular ECG and appropriate treatment is essential to avoid life-threatening arrhythmias [20].

Hypertension

Hypertension is very common after initiation of anti-VEGF therapy by multi-targeted tyrosine kinase inhibitors (sunitinib, sorafenib, axitinib, cediranib, telatinib, etc.) or monoclonal antibodies (bevacizumab). Different mechanisms of action are involved in the rapid increase in blood pressure including vasoconstriction caused by the inhibition of the VEGF pathway and a decrease in nitric oxide levels and endothelial cell apoptosis, which causes a reduction in capillaries and increase overall vascular resistance [21, 22]. Hypertension is usually reversible within 2 weeks of treatment discontinuation.

It is important that the patient is informed that targeted drugs, especially those called angiogenesis inhibitors, can raise blood pressure to the point that specific medication may be needed. It may be useful to educate the patient about monitoring his blood at home so that any onset of hypertension is quickly reported to the nurse or to the treating physician.

Venous Thromboembolic Disease

Drugs such as thalidomide and erlotinib are associated with an increased incidence of venous thromboembolism events, probably due to an increased platelet aggregation and a direct effect on the endothelium.

Prophylactic measures for cardiovascular health include before all the identification of a risk factor and an early referral to a cardiologist. Cancer patients indeed often underestimate cardiovascular risk factors. They should be informed that cardiovascular monitoring is required during and after anticancer treatment. Early involvement of a cardiologist should be encouraged in patients with a pre-existing heart condition such as hypertension, hypercholesterolaemia, type II diabetes, and hypertriglyceridemia. Prior to cancer treatment initiation, cardioprotective measures or modifications to the proposed treatment regimen should be proposed to individuals at high risk. Any anticancer agent should be immediately discontinued at occurrence of a cardiovascular event such as a significant decrease in LVEF or a significant prolongation of the QTc (>500 ms.) [23].

Oral and Upper Gastrointestinal Side Effects

Xerostomia (dry mouth) and dysgeusia (taste loss or disturbance), stomatitis, and mucositis (oral ulceration) are common with mTOR inhibitors such as everolimus (Afinitor®) or temsirolimus (Torisel ®). Stomatitis refers to painful inflammation of the mucous lining of the mouth, whereas mucositis is rather a painful inflammation and ulceration of the mucous membranes lining the digestive tract [24]. Dysgeusia affects almost half of the patients. A decrease in the perception of acid taste is noticed, and an increase in the perception of sweet taste is observed. The modification of bitter and salty tastes is less frequent. Red and infrared low-level laser therapy (LLLT) can partially prevent oral mucositis and also significantly reduce pain, severity, and duration of symptoms [25].

Prophylactic measures include:

  • Regular use of mouthwashes.

  • Advise eating soft, creamy, and unctuous foods.

  • Avoid irritant food: dry, hard, too salty, too spicy, and acidic foods, alcohol, and soft drinks.

  • Moisturising with ice, the use of a fogger, and artificial saliva can be helpful to treat xerostomia.

  • Sucking acidulous and mint candies may help reduce the feeling of dry and pasty mouth.

  • Taking a spoon of cream at the beginning of the meal to help swallow.

  • Rinse the mouth with mouthwashes or acidulous sparkling water (sparkling water + lemon juice) before each meal to enhance the taste of food in case of dysgeusia.

Gastrointestinal perforation is rare and has been reported in association with targeted agents, with the highest rate being with bevacizumab [26]. Gastrointestinal perforation is an indication for immediate discontinuation of therapy.

The most important prophylactic measure is to conduct an in-depth anamnesis before starting the treatment. Treating physician and nurse should pay specific attention on history of past diverticulitis or ulcers, previous radiation exposure, recent sigmoidoscopy or colonoscopy, gastrointestinal obstruction, and multiple previous surgeries.

Diarrhoea is the most common side effect of targeted drugs. This adverse event has been often described with tyrosine kinase inhibitors. The pathophysiological mechanism is secretory by inhibition of EGFR effects on chloride secretion. The management of diarrhoea is essential because of its negative impact on social life and the potentially life-threatening outcomes.

Treatment and Management

Mild diarrhoea may be managed with diet to decrease the frequency of stools. A BRAT (banana, rice, apples, toast) diet can be helpful [27].

Loperamide remains the standard therapy for uncomplicated cases. Chronic low- to intermediate-grade (Grade 1–2) symptoms can be managed with continued loperamide. Early recognition of the warning signs of complicated cases of diarrhoea should be performed. In some aggressive cases, the addition of antibiotics is necessary [28]. Dose adjustments of the anticancer agent or even discontinuation is required for Grade 3 or Grade 4.

Prophylactic measures include:

  • Maintaining an abundant liquid and salt intake. Ideally the drinks should contain starches and/or sugars, sodium, and some potassium. Molasses and other forms of raw sugar can be used; they contain more potassium than white sugar. The WHO advises a home-made oral rehydration solution: stir a mixture of 1 L of water with 2.5 mL (1/2 level teaspoon) of salt and 30 mL (6 level teaspoon) of sugar until dissolution. Traditional remedies such as carrot soup, rice water, gruels (diluted mixtures of cooked cereals and water), weak tea, and green coconut water are suggested.

  • Encouraging to keep dietary measures and avoid drug interactions.

  • Avoiding diets high in fibre or lactose that may aggravate diarrhoea.

Weight Loss

Weight loss may result from a loss of appetite caused by cancer such as from treatment-related nausea, vomiting, dysgeusia, diarrhoea, pain, and mechanical obstruction, among others. Anorexia can result from the loss of appetite. The related symptoms are fatigue, weakness, and distress. They have a negative impact on health-related quality of life. In case of severe cachexia, pharmacologic intervention may be required.

Recommendations and Prophylactic Measures

Different screening and assessment tools are available. The MSTC (malnutrition screening tool for cancer patients) is appropriate for nurses [29]. The MNA (Mini Nutritional Assessment) is a practical tool for identification of nutritional status in geriatric practice [30].

A simple nutritional assessment programme and early counselling by a dietitian are essential to guide nutritional support and to alert the physician to the need for intervention [31]. Nurses should advise patients to keep at least three daily meals, preferably six small meals to split the intake and decrease the quantities. They are advised to eat in a calm, friendly place, at usual times, to adapt cutlery, to remove bad smells, and to adapt the textures of food. Rich food adapted to the tastes is preferable while avoiding hot or spicy food.

Fatigue and Metabolic Toxicities

Fatigue is considered by cancer patients as the most impacting side effect on their quality of life. It is a major cause on non-adherence to treatment, and it may compromise the efficacy of the treatment [32]. Fatigue results from multiple causes. It can be cancer-related, treatment-related, and, as often seen with targeted therapies, related to other conditions including anaemia, hypothyroidism, sleep disturbance, depression, or pain [33].

Recommendations and Prophylactic Measures

It is important to understand the plausible underlying causes of fatigue before providing any recommendation. Hypothyroidism is a very common side effect of patients treated with TKIs. Detection and treatment of pre-existing hypothyroidism before starting TKI treatment are advised. Initially monthly TSH dosage should be performed, but there is no clear consensus on the frequency of thyroid function monitoring. Hyperglycaemia is a very common side effect of the mTOR inhibitors [33]. Before initiating mTOR treatment, the monitoring of the fasting serum glucose is indicated and periodically thereafter.

Treatment and management of fatigue should be based on daily assessment (using reliable and simple tools), patient information, identification and treatment of causal aetiologies, anti-inflammatory therapy when needed, and education and psychological support.

Adherence to Treatment: An Indicator of the Patient’s Empowerment

Therapeutic education is a major component of building a strong therapeutic alliance with the patient, and as such it is a very important part of the nurse role. A therapeutic alliance is built around and in agreement with the educated person. It includes an assessment of needs, available resources, and educational objectives or goals with a choice of tools, intervention planning, and evaluation.

Concretely, optimising a safe and efficient administration of an oral anticancer therapy starts with an exhaustive information and education plan. It serves the purpose of securing that the patient knows and understands his disease and his treatment, as well as the importance of taking the pills. Counselling how to take the drugs safely and how to recognise and to manage side effects is a key element to provide patients with the necessary skills to manage their treatment in a complete autonomy. The adherence process includes tools such as notebooks, folders, computer applications, and smart goal choices, among others. Too much information, however, does not guarantee an optimal adherence. To trigger an action consistent with health, the information must either adhere to the beliefs and representations of the patient or change them [34]. Hence, nurses have to adapt the information to each individual patient, information being not only to talk but also, if not more, to listen to the patients. Ask patients open-ended questions because these are more likely to uncover patients’ concerns and help determine what the patients might need. When needed, the patients should be referred to specialised colleague’s psychologist, dietitians, physicians, and general practitioners. In the end it is about tailoring the process to each individual patient [35].

A prior assessment is essential. In order to ensure the patient’s adherence to the treatment, the multidisciplinary group has to assess the ability (cognitively, psychologically) of the patient to take his/her treatment appropriately and follow the recommendations and after that to propose appropriate supportive care. An exhaustive exchange of information between the care team and the patient will open to a relationship of trust indispensable to an adherence process. In addition, healthcare professionals should keep in mind that the daily administration schedule impacts on compliance, less frequent dosing regimens resulting in better compliance across a variety of therapeutic classes [36].

General Recommended Information for Establishing an Education Programme

According to Mc Cue, a comprehensive oral anticancer education should contain the following information: drug and indication, dose, dosing schedule, start date, administration, what to do for missed doses, food and drug interactions, side effects and management, clinic contact information, and safe handling instructions [37].

The Multinational Association of Supportive Care in Cancer (MASCC) has developed an Oral Agent Teaching Tool (MOATT) that includes four steps to help patient education [38]. This tool is available online at http://www.mascc.org/MOATT. These steps are (I) key assessment questions, (II) patient education, (III) drug-specific education, and (IV) evaluation. These steps focus on special considerations health professionals might have when assessing, educating, and evaluating patients receiving oral agents for cancer is considered.

Key Assessment Questions

When educating a patient, it is recommended to adapt the teaching to accommodate special considerations such as age, feeding tubes, vision problems/colour blindness, dietary issues, and mental problems (dementia, depression, cognitive impairments).

The key assessment questions proposed by MOATT are related to what the patient has been told and knows about this treatment plan with oral medication. It secures that the patient knows that these oral agents are for cancer and are taken by mouth. The patient has to be asked about what other medications or pills he/she is taken by mouth. It is advised to go over the list of patient medicines prescribed or not, herbs, complementary, and other treatments, with the patient. A particular interest should be directed towards the ability of the patient to swallow pills or tablets and to understand the concerned problems. The ability of the patient to read the drug label/information sheet and to safely handle the medicines, bottles, or packages needs to be evaluated. To find out if there were any problems taking the medicine or any other event such as adverse events, the following question is suggested: “Have you taken other pills for your cancer?” “Are you experiencing any symptoms that would affect your ability to keep down your pills, for example, nausea or vomiting?” In some countries patients can have delay in obtaining the oral treatment because of insurance problems. Paying attention and asking the patient if he/she had problems with insurance who interfere with obtaining the medication should be assessed.

Patient Education

Improvement of the patient’s knowledge, skills, and responsibility will be performed by making the patient aware of the importance to consider the following items:

  • Inform any other healthcare provider, doctor, and dentist about the treatment taken.

  • Keep the pills/tablets away from children and pets.

  • Keep the pills/tablets in the original container unless otherwise directed. Do not mix with other pills.

  • Wash hands before and after handling the pills/tablets.

  • Avoid crushing, chewing, cutting, or disrupting pills/tablets unless directed otherwise.

  • Store pills away from heat, sunlight, or moisture as it may degrade the pills/tablets potentially making them less effective.

  • Build a system to take the pills/tablets correctly.

  • Make sure the direction about what to do is known if a dose is missed.

  • Contact a doctor or a nurse immediately if too many pills are taken accidentally or if someone else has taken pills/tablets.

  • Ask a nurse or a pharmacist advice about what should be done with any pills that have not been taken or are outdated.

  • Carry at all time a list of medicines that they are taken, including the cancer pills/tablets.

  • Let the prescribing doctor or the nurse know if they have a problem with paying for or getting the pills/tablets.

  • Plan ahead for travel, refills, and weekends.

Drug-Specific Information

The following references are proposed by the MOATT tool:

This list is not exhaustive and should be completed with any local or national official source of information.

It is recommended that whichever tool is used to educate the patient, the physician and nurse include the following drug-specific information:

  • Drug name (generic and trade).

  • What the drug looks like.

  • Dose and schedule (How many different pills? How many times a day? For how long?).

  • Where to store the drug. The patient needs to have concrete advises. Be specific, for example, away from heat (not in the kitchen), humidity (not in the bathroom), and sun (not on the window sill).

  • What are potential side effects and management of them? Include lab evaluations or any medical tests that will be used for drug monitoring.

  • Are there any precautions?

  • Are there any food interactions?

  • When and whom to call with questions? Give names and phone numbers.

Evaluation

By the end of the education process, patient may have retained only part of the information. It is thus critical to perform an evaluation and review the key points before the patients start the treatment. An easy way to conduct that evaluation is to have the patient and/or caregiver answer the following questions to ensure that they understand what information has been given:

  • What is/are the name(s) of your cancer pill(s)/tablet(s)?

  • At what time(s) of the day will you take your cancer pill(s)/tablet(s)?

  • Does it matter if you take this pill(s)/tablet(s) with food or not?

  • Where do you plan to keep it?

  • When do you call the doctor or nurse?

  • Do you have other questions?

  • When is your next appointment?

  • Who should you contact in case of problems?

Psychological Aspects

The needs of any cancer patient will evolve over the different psychological stages according to their personality, to their representations, as well as to their beliefs and experience. Distress is frequently related to the uncertainty of the disease. Difficulty in facing the disease and complying to the treatment is very often a consequence of experiencing side effects that alter the quality of life.

Nurses play a key role supporting the patients in their coping process regarding the repercussions of the disease and treatments in their daily life and detecting any frailty the patient might have. The use of the Distress Thermometer might be helpful to assess distress [39]. Prompt reference to a psycho-oncologist is required when distress is identified.

Summary

Several oral targeted therapies effectively prolong the duration and the quality of life. However, because these drugs are administered over a long period of time, patients have to face with side effects that can severely affect their quality of life. Preventive and symptomatic measures are key to optimise treatment compliance and improve quality of live. Management of these associated side effects has become a central role of nursing care. This engages the nurse to support the patient in coping with his treatment plan. This requires adapted information and personalised education throughout all the treatment plan. This unfortunately can be standardised until a certain level only. Indeed, it is essential to take into account the personality of the patient and the factors that influence informative and educational support over time.

Finally, there is space for an appropriate care that takes into account various factors of influence. There is the place for a clinical sense in the support role which includes the adapted information and the education in a process of therapeutic alliance, in order to make the patient becomes an actor in his/her treatment plan. This is the primary function of a multidisciplinary and multi-professional team in which each discipline and health professional takes care of the patient with the knowledge of his expertise.