Sutent Therapy Management

SUTENT® AEs are well-characterised, so they can be anticipated and managed early in treatment.1

Common AEs in a pivotal Phase III trial with SUTENT® vs. IFN-α (≥20% in any group)1,2

Together with patient education, measures to prevent and manage adverse events (AEs) associated with SUTENT® therapy are critical for effective disease management.

These measures may reduce the need for dose reductions, delays, interruptions or early treatment discontinuations, thereby optimising clinical benefit obtained from SUTENT®1. This guidance provides advice to support you in the prevention, identification and treatment of a selection of common adverse event AEs associated with SUTENT®, with the aim of reducing their severity and improving treatment tolerability.

Please see the Summary of Product Characteristics for full safety information and information on the prevalence of AEs1 

Please click through the menu below to see how to manage some of the most common AEs found in the therapy management guide (this is available to order for free on Medisa). 

  • 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 mouth4
  • Clinically distinct from chemotherapy-related stomatitis – the signs are less obvious, but the symptoms are pronounced and appear to extend through the gastrointestinal tract5
  • Often resolves during the 2-week break between cycles, although tends to recur in subsequent cycles6,7

Before starting SUTENT® therapy, help patients to minimise risk/severity of stomatitis by encouraging:5,7

  • 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
Stomatitis AE assessment
Signs and Symptoms  Assessment 

Damage to the mouth area, such as bleeding gums and mouth ulcers5,6

Check if your patient is using any concomitant medicines

General sensitivity in the mouth or alterations to taste7

Assess and stabilise comorbidities8

Experiencing pain, particularly when brushing teeth or eating6

Assess the severity of stomatitis9

 

 

 

 

 

 

 

 

  • 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.

  • Is your mouth sore or painful?

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

  • Does it hurt when you eat certain foods?

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

  • Do your gums bleed when you brush your teeth?

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

In addition to preventative measures, encourage patients to 5,7

  • 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

Patients may also want to consider:5,7,10

  • Aspirin mouthwash (mucilage) as a 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 climates5

Before starting SUTENT® therapy, help patients to minimise the risk/severity of hand-foot skin reactions by encouraging them to 5,11,12 

  • 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 reactions7,9
Signs and Symptoms Assessment
Hand-foot skin reactions usually occur on the palms of hands and soles of feet but may affect other areas Check if your patient is using any concomitant medicines
Look for red, swollen and sensitive skin, tingling sensation or numbness, and blisters, cracks and peeling5,7,11 Assess and stabilise comorbidities8

  • 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 a 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 to5,7,11

  • 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:7,11

  • 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 reactions5. 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.8

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.7

Management strategies for Hand-foot Skin Reactions
Grade  Characteristics Strategy
1

Minimal skin changes or dermatitis (e.g. erythema, oedema or hyperkeratosis) without pain.

Continue at same dose level. Treat with emollient creams and encourage measures to avoid skin irritation.

2

Skin changes (e.g. peeling, blisters, bleeding, oedema or hyperkeratosis) with pain that limits instrumental activities of daily living.

Treat with emollient creams and encourage measures to avoid skin irritation. Consider a SUTENT® dose reduction.

3

Severe skin changes (e.g. peeling, blisters, bleeding, oedema or hyperkeratosis) with pain that limits self-care activities of daily living.

Consider a SUTENT® dose reduction or treatment break until grade ≤1, then resume treatment at a reduced dose.

 

Hypertension that develops while on treatment has been proposed as a potential biomarker for SUTENT® efficacy, so treatment should be maintained at the recommended dose where possible. 17,18

    Cardiovascular AEs

    • ≥20% decrease in left ventricular ejection fraction (LVEF) and LVEF below the lower limit of normal – 2% of patients at all grades1
    • Heart failure has been reported in mRCC clinical trials and in postmarketing experience1
    • SUTENT® has the potential to prolong the QT interval1
    • Arrhythmias – incidence <1% (e.g. bradycardia and torsades de pointes)1,6

    Hypertension

    •            Associated with SUTENT®, typically manifests early (within days/weeks of initiating treatment) and is usually mild to moderate5 (grade 2/3)

    • Help patients to minimise the 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/day13,14
    • Normalise pre-existing hypertension prior to starting SUTENT® therapy1,14
    • Close monitoring is recommended for patients with cardiac risk factors and/ or history of coronary artery disease1
    • Encourage patients to keep a diary of their blood pressure and report any signs of hypertension to staff14

     

    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 treatment1,3,8,9,15,16
    • Monitor and stabilise blood pressure frequently throughout treatment3,8,15
    • Blood pressure should be monitored weekly for the first 4 weeks and monthly thereafter, ideally by patients themselves or in primary care5
    • Perform risk-benefit analysis based on cardiovascular risk factors/ coronary artery disease history1
    • Check if your patient is using any concomitant medicines
    • Assess and stabilise comorbidities8
    • Assess severity of hypertension9

    • 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 instance13. Some patients may require SUTENT® dose adjustment or treatment break based on the severity of their cardiovascular AEs/hypertension1,6,15. 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.1,3

    Hypertension

    Temporarily suspend SUTENT® in patients with severe uncontrolled hypertension that is not reversed with medical management – treatment may resume once hypertension is controlled.1,8

    If prescribed, antihypertensive treatment may need to be reduced during off-treatment periods and stopped altogether when not taking SUTENT®, to prevent postural hypotension.5

    Management strategies for Hypertension and other Cardiovascular Events
    Grade Characteristics Strategy       
    1

    Prehypertension (systolic BP 120–139 mmHg or diastolic BP 80–89 mmHg)

    Continue at same dose level

    2

    Stage 1 hypertension (systolic BP 140–159 mmHg or diastolic BP 90–99 mmHg); medical intervention indicated; recurrent or persistent (≥24 hours); symptomatic increase by >20 mmHg (diastolic) or to >140/90 mmHg if previously within normal limit; monotherapy indicated. 

    Continue at a same dose level, except in the presence of:

    • Asymptomatic decrease in LVEF by an absolute value of 20% and below lower limit of normal

    OR

    • Non-urgent ventricular paroxysmal dysrhythmia requiring intervention
    Interrupt SUTENT® therapy until grade ≤1 THEN resume at -1 dose level
    3

    Stage 2 hypertension (systolic BP ≥160 mmHg or diastolic BP ≥100 mmHg); medical intervention indicated; more than one drug or more intensive therapy than previously used/indicated. 

    Interrupt SUTENT® therapy until grade ≤1 or return to baseline.

    Resume at -1 dose level.
    4

    Life-threatening consequences (e.g. malignant hypertension, transient or permanent neurologic deficit, hypertensive crisis); urgent intervention indicated

    Discontinue

     

    Gastrointestinal AEs may include constipation, diarrhoea, indigestion, bloating, swallowing difficulties, nausea or vomiting and discomfort or bleeding in the mouth or rectum.1,5,7,13

    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 consistency13,14
    • Anti-emetics can be given prophylactically to limit treatment-related nausea and vomiting7
    • Follow the advice from a dietician about calorie intake before and during SUTENT® treatment8

    Weight loss has been observed and can be a symptom of loss of appetite, generally caused by altered taste, tender mouth or indigestion5. Symptoms generally resolve after a week off treatment, but weight loss can be treatment-limiting5

    • Confirm the presence of gastrointestinal symptoms
    • Check if the patient is using any concomitant medicines
    • Assess and stabilise comorbidities8
    • Assess the 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 an 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 recommended7.  SUTENT® dose interruptions/ reductions from the recommended 50 mg daily dosing can be avoided or minimised using therapy management, helping patients to gain optimal benefit7. Reinforce preventative advice and provide supporting advice to patients if they suffer from gastrointestinal AEs

    Nausea and vomiting 5,7

    Encourage patients to:

    • Use common anti-emetics to relieve nausea and vomiting
    • Eat small, more frequent meals if nauseated
    Nausea and Vomiting Grading
    Grade Nausea Presentation Vomiting Presentation 
    1 Loss of appetite without alteration in eating habits 1–2 episodes (separated by 5 minutes) in 24 hours
    2 Oral intake decreased without significant weight loss, dehydration or malnutrition 3–5 episodes (separated by 5 minutes) in 24 hours
    3 Inadequate oral caloric or fluid intake; tube feeding, total parenteral nutrition or hospitalisation indicated ≥6 episodes (separated by 5 minutes) in 24 hours; tube feeding, total parenteral nutrition or hospitalisation indicated
    4   Life-threatening consequences; urgent intervention indicated

     

    Diarrhoea 5,7,13

    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
    Diarrhoea Grading
    Grade  Presentation
    1 Increase of <4 stools per day over baseline; mild increase in ostomy output compared to baseline
    2 Increase of 4–6 stools per day over baseline; moderate increase in ostomy output compared to baseline
    3 Increase of ≥7 stools per day over baseline; incontinence; hospitalisation indicated; severe increase in ostomy output compared to baseline; limiting self-care activities of daily living
    4 Life-threatening consequences; urgent intervention indicated
    Management strategies for diarrhoea
    Grades Strategy 
    1 & 2 Continue at same dose level. Oral hydration in small amounts at a time + anti-diarrhoeal medications
    3 & 4

    Interrupt SUTENT® therapy until grade ≤1 Resume SUTENT® dose at -1 dose level (12.5 mg) in subsequent cycles in cases of grade 3 or 4 diarrhoea

    Other gastrointestinal disorders treatment options 

    Blood disorders/dyscrasias such as neutropaenia, thrombocytopaenia, anaemia and leukopaenia have been associated with SUTENT® treatment.1

    Neutropenia and thrombocytopenia: 

    Typically manifest early, during the first treatment cycle, without progression during later cycles. 8,19

    SUTENT®-induced neutropaenia and thrombocytopaenia usually resolve during the 2-week treatment break. 6,8,19

    Before starting SUTENT®, advise patients on:

    • The importance of good hygiene and diet. 8
    • Basic guidelines to minimise the risk of infection (e.g. washing hands).6

    Carry out a  blood count to assess for blood disorders and abnormal blood counts 1,19

    • 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 the patient is using any concomitant medicines
    • Assess and stabilise comorbidities8
    • Assess the severity of blood disorders 

    • Signs of infection/elevated temperature
    • Bruising (thrombocytopaenia)
    • Fatigue, pale skin (anaemia)

      • 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 neutropaenia.

      • Are you bruising or bleeding more easily than normal?

      This may indicate thrombocytopaenia.

      • 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 anaemia.

      • 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.

      Neutropaenia

      Typically, the neutropaenia associated with SUTENT® treatment requires no intervention -  blood counts tend to recover during the 2-week treatment break between cycles.6,7

      Anaemia

      Grade 3/4 anaemia 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.6,7

      Management strategies for blood disorders
      Grade Presentation  Strategy 
      1 & 2

      Grade 1:ANC ≥1.5 to <2.0 x 109/L

      Grade 2:  ANC ≥1.0 to <1.5 x 109/L 

      Continue at same dose level
      3 ANC ≥0.5 to <1.0 x 109/L  Withhold dose. When grade ≤2, resume treatment at original dose*
      4 ANC <0.5 x 109/L Withhold dose. When grade ≤2, resume treatment at -1 dose level*

      *Recurring grade 3/4 neutropaenia or thrombocytopaenia persisting for at least 5 days and/or neutropaenic fever/bleeding signs may require dose/schedule changes. 7

       

      Includes conditions such as hand-foot skin reactions, rash, dry skin, nail modifications and skin/hair discolouration.1,7 This often occurs within the first 6 weeks of treatment (typically in Weeks 3 and 4).7

      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 clothes7. Before starting SUTENT® therapy, help patients to minimise risk/severity of skin and hair changes – encourage them to 7,8

      • 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 discolouration1,7
      • Hair depigmentation – growing hair may become grey or white during the course of treatments 7,23
      • Small subungual haemorrhages – small linear brown or black lines located under the distal portion of the nails23

      • Check if the patient is using any concomitant medicines
      • Assess and stabilise comorbidities8
      • A bilirubin level may be required to distinguish between SUTENT® - induced skin discolouration and jaundice due to liver disease or biliary obstruction7

      • Are you noticing any skin or hair changes, such as a 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:5,7,13

      • 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 a 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. 

      Grading for Rashes9
      Grade  Presentation
      Grade 1 Macules/papules covering <10% body surface area with or without symptoms (e.g. pruritus, burning, tightness)
      Grade 2 Macules/papules covering 10–30% body surface area with or without symptoms (e.g. pruritus, burning, tightness) that limit instrumental activities of daily living.
      Grade 3 Macules/papules covering >30% body surface area with or without associated symptoms that limit self-care activities of daily living. 

       

      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.5,19

      Fatigue

      Typically manifests early, within days or weeks of SUTENT® treatment initiation19.  May be transient, resolving as the patient responds to treatment13.  Can be treatment-related as SUTENT® can cause hypothyroidism or anaemia, which result in fatigue1,24

       

      Hypothyroidism

      Is often under-diagnosed and may be the underlying cause of fatigue1,5,24. Typically takes time to manifest (usually months), although occasionally the time of onset can be within weeks of SUTENT® treatment initiation5,7

      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 initiation1. In order to minimise the impact of fatigue, provide patients with the following lifestyle modification advice5,7:

      • 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 clinic5.

      Hypothyroidism

      Symptoms of hypothyroidism include5:

      • 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 the patient is using any concomitant medicines
      • Assess and stabilise comorbidities8
      • In Cycles 1–3, monitor for the impact of fatigue on quality of life19
      • Every 2–3 cycles check for anaemia, depression and hypothyroidism – treat as appropriate19
      • 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 thereafter7

      "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.5,19

      • 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 the severity of fatigue/hypothyroidism7. The severity of the symptoms needs to be weighed up against the benefits of maintaining the recommended SUTENT® dosing schedule.

      Fatigue

      Determine if fatigue is disease or drug-related. Alternative causes for fatigue should be ruled out – fatigue may be exacerbated by dehydration, hypercalcaemia, anaemia or depression. Reinforce preventative advice and further encourage patients to7:

      • Maintain normal work and social schedules, but to take breaks when necessary13,14
      • Carry out light physical exercise in order to reduce fatigue levels and to help induce sleep5,14

      Hypothyroidism

      • Thyroid-stimulating hormone levels tend to improve during the 2-week treatment break
      • Hypothyroidism can be managed with thyroid hormone replacement therapy5,6

      Ensure the cause of a patient’s fatigue is diagnosed and treated if necessary

      ​ Grades and management strategies for hypothyroidism ​
      Grade Presentation
      1 Asymptomatic – clinical or diagnostic observations only
      2 Symptomatic
      3 Severe symptoms, hospitalisation
      4 Life-threatening consequences

      Overt hypothyroidism, defined as elevated TSH and a low T4 level, can be treated with thyroid hormone replacement.

      AEs, adverse events

      References

      1. SUTENT® Summary of Product Characteristics. Pfizer. Available at: www.medicines.org.uk.
      2. Motzer RJ, et al. J Clin Oncol 2009;27:3584–3590.
      3. Ravaud A. Ann Oncol 2009;20:i7–i12.
      4. National Cancer Institute. NCI Dictionary of Cancer Terms. Stomatitis. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/ def/stomatitis. Accessed: April 2020.
      5. Pyle L, et al. Cancer Nursing Pract 2008;7:42–47.
      6. Kollmannsberger C, et al. Can Urol Assoc J 2007;1(2Suppl):S41–S54.
      7. Kollmannsberger C, et al. Oncologist 2011;16:543–553.
      8. Roigas J. Eur Urol Suppl 2008;7:593–600.
      9. Common Terminology Criteria for Adverse events v4.03 (CTCAE). Available at: https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/ CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf. Accessed: April 2020.
      10. Guevremont C, et al. Curr Opin Support Palliat Care 2009;3:170–179.
      11. Wood LS, et al. Commun Oncol 2010;7:23–29.
      12. Lacouture ME, et al. Oncologist 2008;13:1001–1011.
      13. Wood LS. Commun Oncol 2006;3:558–562.
      14. Grünwald V, et al. World J Urol 2010;28:343–351.
      15. Schmidinger M, et al. Cancer Invest 2010;28:856–864.
      16. Ravaud A. Oncologist 2011;16(Suppl 2):32–44.
      17. Donskov F, et al. Br J Cancer 2015;113:1571–1180.
      18. Bæk Møller N, et al. Int J Mol Sci 2019;20:E4712.
      19. Négrier S & Ravaud A. Eur J Cancer Suppl 2007;5:S12–S19.
      20. Crawford J, et al. Cancer 2004;100:228–237.
      21. Sekhan SS & Roy V. South Med J 2006;99:491–498.
      22. Gnann JW, et al. Antimicrob Agents Chemother 1998;42:1139–1145.
      23. Robert C, et al. Lancet Oncol 2005;6:491–500.
      24. Torino F, et al. Nat Rev Clin Oncol 2009;6:219–228.

      PP-SUT-GBR-0584. July 2020