• An inflammation of the mucous lining of any of the structures in the mouth, which may involve the cheeks, gums, tongue, lips, throat, and roof or floor of the mouth³
• Clinically distinct from chemo therapy related stomatitis – the signs are less obvious, but the symptoms are pronounced and appear to extend through the gastrointestinal tract⁴
• Often resolves during the 2-week break between cycles, although tends to recur in subsequent cycles ^5,6

• Good oral hygiene, including regular visits to the dentist
• Avoidance of hot, spicy and acidic foods, as well as alcohol
• Eating little and often
• ​​​​​​​Drinking cool liquids and keeping fluid intake high​​​​​​​

Do you get more mouth ulcers than usual?

• Inflammation of the oral cavity and mouth ulcers can be an indication of stomatitis or other oral changes.

• Patients may experience pain, even without physical signs of functional stomatitis.

• Encourage your patients to avoid hot, spicy foods and alcohol.

• Encourage your patients to use gentle toothbrushes and sodium bicarbonate-based mouthwashes.

• Use baby toothpaste, brushes and bicarbonate-based mouthwashes
• Use lip creams/balms
• Eat soft foods that are at room temperature
• Consider cold items that may relieve symptoms, such as frozen pineapple chunks
• Eat with a spoon rather than a fork and drink using a straw

• Aspirin mouthwash (mucilage) as local analgesic (do not swallow; contraindicated in patients who are haematologically compromised  
• Mouthwash containing viscous lidocaine, diphenhydramine, and bismuth subsalicylate or aluminium/ magnesium hydroxide
• Anti-inflammatories
• Nystatin for oral thrush
• Artificial saliva for dry mouth

More pronounced on the feet of active people and in hot climates⁴

Before starting SUTENT  therapy, help patients to minimise risk/severity of hand–foot skin reactions by encouraging them to:^4,10,11

• Wash gently with baby soaps and shampoos
• Regularly apply moisturising emollients (available from chemists)
• Wear cotton or rubber gloves for housework, washing up, etc.
• Keep feet bare or wear cotton socks and comfortable shoes

Visit a chiropodist prior to beginning SUTENT therapy for a podiatry review and to remove calluses

Grading and treating hand–foot skin reactions^6,8

Can you hold a cup of tea? Is wearing shoes unbearable? How have the changes to your skin affected what you can do?

• It is important to assess the severity of hand–foot skin reactions for each individual.

Are you noticing any skin changes, such as change in colour, feel or sensation?

• Encourage your patients to examine their skin regularly and discuss any changes or concerns that they have with you at the clinic and by phone in between visits.

Do you have any skin changes in other areas?

• Remember that skin changes may occur in areas of the body that patients may not want to immediately disclose.

How does your hand–foot skin reaction affect your everyday life?

• The severity and impact of hand–foot skin reactions may differ from patient to patient.

Reinforce preventative advice to patients who suffer from hand–foot skin reactions and further encourage patients to:^4,6,10

• Avoid/reduce activities that put a lot of pressure on the affected areas
• Wear loose, comfortable clothes and shoes, and use gel/soft insoles
• Avoid strong sunlight or extreme heat (including very hot baths)
• Protect tender areas and pressure points with padding, foam absorbents and shock absorbers

Relief from symptoms can be found using:^6,10

• Topical morphine combined with a petroleum jelly based ointment for patients experiencing severe pain
• Moisturising emollient creams and urea-based creams, especially for the feet
• Topical skin adhesives (medical superglue) applied to cracks and painful areas
• Daily foot soaks in lukewarm water with Epsom salts for 20–30 minutes

Some patients may require a SUTENT dose adjustment or treatment break based on the severity of hand–foot skin reactions⁴. The severity of hand–foot skin reactions needs to be weighed up against the benefits of maintaining the recommended SUTENT dose. Once hand–foot skin reactions have resolved, consider re-initiating SUTENT treatment at 50 mg daily.⁷

If a patient believed to have hand–foot skin reactions does not respond to dose interruption or dose reduction, then other diagnoses must be considered.⁶

Hypertension has been proposed as a potential biomarker for SUTENT efficacy, so treatment should be maintained at the recommended dose when possible.^16,17

Cardiovascular AEs

• ≥20% decrease in left ventricular ejection fraction (LVEF) and LVEF below the lower limit of normal – 2.1% of patients at all grades²
• Heart failure has been reported in mRCC clinical trials and in postmarketing experience²
• SUTENT has the potential to prolong the QT interval²
• Arrhythmias – incidence <1% (e.g. bradycardia and torsades de pointes)^2,5

Hypertension

• Associated with SUTENT, typically manifests early (within days/weeks of initiating treatment) and is usually mild to moderate (grade 2/3)⁴

• Help patients to minimise risk of cardiovascular AEs by encouraging them to exercise regularly, control their weight, consider a healthy diet, drink alcohol in moderation and keep their salt intake below 2 g/day^12,13
• Normalise pre-existing hypertension prior to starting SUTENT therapy^2,13
• Close monitoring is recommended for patients with cardiac risk factors and/ or history of coronary artery disease²
• Encourage patients to keep a diary of their blood pressure and report any signs of hypertension to staff¹³

Advise your patients to report any of the following AEs directly and urgently, they should not wait for their next scheduled appointment:

• Shortness of breath
• Extreme fatigue
• swelling of the hands or feet
• persistent headache or dizziness

• Conduct a full cardiovascular assessment, including baseline ECG and LVEF evaluation, and monitor throughout treatment^{1,2,7,8,14,15}
• Monitor and stabilise blood pressure frequently throughout treatment^1,7,14
• Blood pressure should be monitored weekly for the first 4 weeks and monthly thereafter, ideally by patients themselves or in primary care⁴
• Perform risk–benefit analysis based on cardiovascular risk factors/ coronary artery disease history²
• Check if your patient is using any concomitant medicines
• Assess and stabilise comorbidities⁷
• Assess severity of hypertension⁸

Have you taken your blood pressure this week?

• Encourage your patients to monitor their blood pressure and keep a diary of their blood pressure readings.

Have you felt short of breath, very tired or had any swelling of the hands and feet since taking SUTENT?

• These symptoms may be indicative of a cardiovascular AE and will require urgent attention.

Have you had a persistent headache or felt any dizziness since taking SUTENT?

• These symptoms may be indicative of a cardiovascular AE and will require urgent attention

Reinforce preventative advice and further encourage patients to consider non-pharmacological measures in the first instance¹². Some patients may require SUTENT dose adjustment or treatment break based on severity of their cardiovascular AEs/hypertension^2,5,14. The severity of their cardiovascular AEs should be weighed up against the benefits of maintaining the recommended SUTENT dosing schedule.

Cardiovascular AEs

• Interrupt/reduce SUTENT dose in patients with clinical evidence of congestive heart failure if LVEF <50% and >20% below baseline.^1,2

Hypertension

• Temporarily suspend SUTENT in patients with severe uncontrolled hypertension that is not reversed with medical management – treatment may resume once hypertension is controlled.^2,7

If prescribed, antihypertensive treatment may need to be reduced during off-treatment periods and stopped altogether when not taking SUTENT, to prevent postural hypotension.⁴

Gastrointestinal AEs may include constipation, diarrhoea, indigestion, bloating, swallowing difficulties, nausea or vomiting and discomfort or bleeding in the mouth or rectum.^2,4,6,12

Before starting SUTENT therapy, help patients to minimise the risk and severity of gastrointestinal AEs by encouraging them to:

• Adjust their diet – bananas, rice, grated apple and toast can increase stool consistency^12,13
• Anti-emetics can be given prophylactically to limit treatment-related nausea and vomiting⁶
• Follow advice from a dietician about calorie intake before and during SUTENT treatment⁷

Weight loss has been observed and can be a symptom of loss of appetite, generally caused by altered taste, tender mouth or indigestion⁴. Symptoms generally resolve after a week off treatment, but weight loss can be treatment-limiting⁴.

• Confirm the presence of gastrointestinal symptoms
• Check if patient is using any concomitant medicines
• Assess and stabilise comorbidities⁷
• Assess severity of gastrointestinal symptoms

Have you suffered from a loss of appetite since starting treatment? Why do you think this might be?

• This may be due to a variety of reasons, such as nausea, taste changes and pain while eating.

Have you experienced any increase in indigestion, diarrhoea, constipation or flatulence since starting treatment?

• Changes in bowel movements are very common with SUTENT, but symptoms are usually mild-to-moderate.

Have you felt nauseous or been sick since starting treatment?

• Discuss possible reasons for nausea or vomiting, including as an AE of SUTENT.

Patient education regarding nutrition and consultation with a dietician is recommended⁶.  SUTENT dose interruptions/ reductions from the recommended 50 mg daily dosing can be avoided or minimised using therapy management, helping patients to gain optimal benefit⁶. Reinforce preventative advice and provide supporting advice to patients if they suffer from gastrointestinal AEs.

Encourage patients to:

• Use common anti-emetics to relieve nausea and vomiting
• Eat small, more frequent meals if nauseated

Encourage patients to:

• Temporarily discontinue the use of stool softeners or fibre supplements
• Eat and drink often in small amounts
• Drink plenty of liquids (approx. 2–2.5 L/day, in small amounts at a time) and avoid drinking fluids with meals and for 1 hour after meals
• Avoid spicy, high-fibre and fatty foods, and caffeine
• Use anti-diarrhoeal treatments (e.g. loperamide), as required
• Eat live yoghurt and other acidophilus products
• Keep a diary to help monitor their bowel movements and highlight any factors that may make symptoms worse
• Apply barrier creams (e.g. Sudocrem, Drapolene, Vaseline, aloe vera) to areas of skin at risk of becoming dry or broken
• Use local analgesia (e.g. lidocaine gel) on painful areas of skin

Other gastrointestinal disorders treatment options:

• Dyspepsia: Peppermint and antacids, according to local prescribing policy 
• Abdominal pain: Analgesia and antispasmodics
• Constipation: Fluids, diet, exercise and mild laxatives

Blood disorders/dyscrasias such as neutropenia, thrombocytopenia, anemia and leukopenia have been associated with SUTENT treatment.²

• Typically manifest early, during the first treatment cycle, without progression during later cycles. ^7,18 
• SUTENT-induced neutropenia and thrombocytopenia usually resolve during the 2-week treatment break. ^5,7,18

Before starting SUTENT, advise patients on:

• The importance of good hygiene and diet.⁷
• Basic guidelines to minimise the risk of infection (e.g. washing hands).⁵

• Signs of infection/elevated temperature
• Bruising (thrombocytopenia)
• Fatigue, pale skin (anemia)

Carry out a complete blood count to assess for blood disorders and abnormal blood counts^2,18

• This should be performed before initiating SUTENT and at the start of each treatment cycle
• Full blood count monitoring is recommended every 3 weeks, work with GP to carry out blood counts locally
• Check if patient is using any concomitant medicines
• Assess and stabilise comorbidities⁷
• Assess severity of blood disorders

Have you felt ill or had a temperature recently?

• Any incidence of a temperature over 38°C and other signs of infection may indicate underlying neutropenia.

Are you bruising or bleeding more easily than normal?

• This may indicate thrombocytopenia.

Have you been very tired recently, had any breathlessness, had faster heart rate than normal, experienced rushing sounds in the ears, been feeling faint, experienced headaches or had pale skin?

• These symptoms may indicate anemia.

How do the blood disorders affect your everyday life?

• The severity of symptoms and the impact may differ from patient to patient.

Provide supporting advice to patients with blood disorders.

Neutropenia

Typically, the neutropenia associated with SUTENT treatment requires no intervention -  blood counts tend to recover during the 2-week treatment break between cycles.^5,6

Anemia

Grade 3/4 anemia usually does not require dose modification, but should be treated with iron supplementation or blood transfusions if severe or life threatening. Erythropoietin-stimulating agents should be used with caution owing to potential risks and toxicities associated with these drugs.^5,6

Recurring grade 3/4 neutropenia or thrombocytopenia persisting for at least 5 days and/or neutropenic fever/bleeding signs may require dose/schedule changes. ⁶

Includes conditions such as hand– foot skin reactions, rash, dry skin, nail modifications and skin/hair discolouration.^2,6 This often occurs within the first 6 weeks of treatment (typically in Weeks 3 and 4).⁶

Inform patients of the potential for reversible depigmentation of the hair and skin. Patients should avoid hot showers, use sun protection and wear loose-fitting cotton clothes⁶. Before starting SUTENT therapy, help patients to minimise risk/severity of skin and hair changes – encourage them to:^6,7

• Avoid hot showers, use sun protection and wear loose-fitting cotton clothes
• Reduce pressure on skin areas
• Take good care of their skin – wash gently with baby soaps and shampoos, and regularly apply moisturising emollients (available from chemists)
• Use anti-itch and anti-dandruff shampoos, hydrocolloid bandages, thick-soled shoes, local corticoid cream, Vitamin A cream and urea cream

• Skin colour changes – a yellowish, reversible discolouration^2,6
• Hair depigmentation – growing hair may become grey or white during the course of treatment^6,22
• Small subungual haemorrhages – small linear brown or black lines located under the distal portion of the nails²²

• Check if patient is using any concomitant medicines
• Assess and stabilise comorbidities⁷
• A bilirubin level may be required to distinguish between SUTENT - induced skin discolouration and jaundice due to liver disease or biliary obstruction⁶

Are you noticing any skin or hair changes, such as change in colour, feel or sensation?

• Encourage your patients to examine their skin and hair regularly, and discuss any changes or concerns that they have with you at the clinic or by telephone in between visits.

How are you managing your skin and hair changes? Do they affect your everyday life?

• The severity of the symptoms and their physical and psychological impact may differ from patient to patient

Provide supporting advice to patients if they suffer from skin and hair changes
Patients with dry skin/rash:^4,6,12

• Can benefit from moisturising creams and ointments, which are usually sufficient to alleviate dryness
• Should change to a fragrance-free soap or liquid shower gel – If their dry skin/rash worsens, prescription-strength emollients may be needed 
• If affecting the scalp, they should use an anti-dandruff shampoo to help relieve discomfort

Patients with severe genital rash should be referred to a dermatologist who can prescribe an appropriate treatment after ruling out a yeast or bacterial infection.

The severity of the skin and hair changes need to be weighed up against the benefits of maintaining the recommended SUTENT dosing schedule. 

Check for underlying factors that may cause fatigue such as hypothyroidism, anaemia, depression, dehydration, poor diet, lack of exercise, pain, insomnia, chronic illness and appetite.^4,18

Fatigue

Typically manifests early, within days or weeks of SUTENT treatment initiation¹⁸.  May be transient, resolving as the patient responds to treatment¹².  Can be treatment-related as SUTENT can cause hypothyroidism or anaemia, which result in fatigue^2,23

Hypothyroidsim

​​​​​​​Is often under-diagnosed and may be the underlying cause of fatigue^2,4,23. Typically takes time to manifest (usually months), although occasionally the time of onset can be within weeks of SUTENT treatment initiation^4,6.

• Identify and resolve underlying factors that may affect the level of fatigue, including haemoglobin levels, thyroid function and pain control⁴. Assess baseline thyroid function before treatment initiation². In order to minimise the impact of fatigue, provide patients with the following lifestyle modification advice^4,6:
• Take short naps or breaks when necessary
• Accept help from others
• Take regular light exercise
• Try to maintain a normal sleep pattern
• Use relaxation techniques, e.g. read a book or listen to music
• Make use of treatment breaks

Fatigue

Changes in your patient’s activities and attentiveness on the phone or in the clinic⁴.

Hypothyroidism

Symptoms of hypothyroidism include⁴:

• Fatigue, swelling around the eyes, dry skin, shortness of breath and feeling cold
• Several of these symptoms are caused directly by SUTENT, and are not necessarily related to hypothyroidism

• Confirm the presence of fatigue and/or hypothyroidism
• Check if patient is using any concomitant medicines
• Assess and stabilise comorbidities⁷
• In Cycles 1–3, monitor for impact of fatigue on quality of life¹⁸
• Every 2–3 cycles check for anaemia, depression and hypothyroidism – treat as appropriate¹⁸
• Encourage patients to rate their fatigue on a numeric scale, where 0 = ‘no fatigue’ and 10 = ‘worst fatigue imaginable’
• Thyroid profile should be measured at baseline on Day 1 of each cycle, for four cycles, and every 3 months thereafter⁶

Have you been feeling more tired than usual since you started taking SUTENT?

• It is important to have educated your patient to tell you as soon as an AE, like fatigue, becomes troublesome so that the most appropriate supportive care can be promptly provided.

Do you do any exercise?

• Light physical exercise may reduce fatigue levels and help your patient get a better night’s sleep

At what time of the day do you take SUTENT?

• Some patients cope better if they take SUTENT in the evening, while others have difficulty sleeping after a night-time dose. There is no ‘correct’ time, but once a pattern has been established, medicine should be taken at roughly the same time every day.

How does your fatigue and/or hypothyroidism affect your everyday life?

• The severity and impact of fatigue/ hypothyroidism may differ from patient to patient.

Patients may require SUTENT dose adjustment or treatment break based on severity of fatigue/hypothyroidism⁶. Severity of the symptoms need to be weighed up against the benefits of maintaining the recommended SUTENT dosing schedule.

Kollmannsberger C, et al. Oncologist 2011;16:543–553.

Fatigue

Determine if fatigue is disease or drug-related⁶. Alternative causes for fatigue should be ruled out – fatigue may be exacerbated by dehydration, hypercalcaemia, anaemia or depression⁶. Reinforce preventative advice and further encourage patients to:

• Maintain normal work and social schedules, but to take breaks when necessary^12,13
• Carry out light physical exercise in order to reduce fatigue levels and to help induce sleep^4,12

Hypothyroidism

• Thyroid-stimulating hormone levels tend to improve during the 2-week treatment break
• Hypothyroidism can be managed with thyroid hormone replacement therapy^4,5
• Ensure the cause of a patient’s fatigue is diagnosed and treated if necessary