guidelines for the management of presentations in adults 2014 onc docs/neyhca... · 2015. 4....

Guidelines For The Management of Acute Oncology

Presentations in Adults 2014

Malignant Ascites Pleural Effusion

Pericardial Effusion Lymphangitis Carcinomatosa

Superior Vena Cava Obstruction Hypercalcaemia

Malignant Spinal Cord Compression Cerebral Space Occupying Lesion

Radiation Induced Dermatitis Radiation Induced Pneumonitis

Chemotherapy and/or Radiotherapy induced Acute Mucositis Chemotherapy and/or Radiotherapy induced Diarrhoea

Chemotherapy and/or Radiotherapy induced Nausea & Vomiting Management Algorithm for SIADH in Oncology

| Acute Oncology CEG Guidelines for the Management of Acute oncology Presentations Version 2.0a January 2014

Version Control

This is a controlled document please destroy all previous versions on receipt of a new version.

Review Date: September 2015

Version Date Issued Review Date Brief Summary of Change Owner’s Name

1.0 July 2011 July 2013 Original Draft Network Acute Oncology Group

1.1 August 2011 August 2013 First Draft Network Acute Oncology Group

1.2 September 2011

June 2012 Final Document Network Acute Oncology Group

2.0 June 2012 June 2014 Added Radiation induced pneumonitis and radiation induced dermatitis

Acute Oncology Clinical Expert Group

2.0a January 2014 September 2015

Date Revised added chemo and radiotherapy induced Mucositis, diarrhoea, nausea & vomiting and SIADH

Acute Oncology Clinical Expert Group

For the latest version of these guidelines please see the NEYHCA (Cancer) website Please press control and click on the link below

http://www.hyccn.nhs.uk/NetworkGuidelinesAndPublications/acuteoncology.htm

Acute Oncology CEG Guidelines for the Management of Acute Oncology Presentations Version 2.0a January 2014 |

Contents Version Control .............................................................................................................................. 2

Contents ......................................................................................................................................... 3

1. Management of Malignant Ascites .............................................................................................. 6

1.1 Introduction ............................................................................................................................. 6

1.2 Symptoms and Signs ................................................................................................................ 6

1.3 Investigations ........................................................................................................................... 6

1.4 Management ............................................................................................................................ 6

1.5 Outcome ................................................................................................................................... 6

2. Management of Malignant Pleural Effusion ................................................................................ 7

2.1 Introduction ............................................................................................................................. 7


2.21 Signs of effusion ................................................................................................................. 7

2.3 Investigations ........................................................................................................................... 7

2.4 Management ............................................................................................................................ 7

2.41 Emergency presentations ................................................................................................... 7

2.42 Non-emergency presentations ........................................................................................... 8

3. Management of Pericardial Effusion ............................................................................................ 9

3.1 Introduction ............................................................................................................................. 9


3.3 Investigations ........................................................................................................................... 9

3.4 Management ............................................................................................................................ 9

3.5 Outcome ................................................................................................................................... 9

4. Management of Lymphangitis Carcinomatosa .......................................................................... 10

4.1 Introduction ........................................................................................................................... 10

4.2 Diagnosis ................................................................................................................................ 10

4.3 Management .......................................................................................................................... 10

4.4 Anti-cancer treatment ........................................................................................................... 10

4.5 Symptomatic treatment ......................................................................................................... 10

4.6 Pharmacological treatment ................................................................................................... 10

4.61 Opioids .............................................................................................................................. 11

4.62 Benzodiazepines .............................................................................................................. 11

4.7 General symptomatic measures ............................................................................................. 11

5. Management of Superior Vena Cava Obstruction ..................................................................... 12

5.1 Introduction ........................................................................................................................... 12

5.2 Symptoms and Signs .............................................................................................................. 12

5.3 Investigations ......................................................................................................................... 12

5.4 Management .......................................................................................................................... 12

5.5 Recurrent superior vena cava obstruction............................................................................. 12

5.6 Outcome ................................................................................................................................. 12

6. Management of Hypercalcaemia ................................................................................................ 13

6.1 Introduction ........................................................................................................................... 13

6.2 Symptoms and signs ............................................................................................................... 13

6.3 Investigations ......................................................................................................................... 13

6.4 Management .......................................................................................................................... 13

6.5 Outcome ................................................................................................................................. 13


7. Malignant Spinal Cord Compression .......................................................................................... 14

7.1 Introduction ........................................................................................................................... 14

7.2 Symptoms and signs ............................................................................................................... 14

7.3 Investigations ......................................................................................................................... 14

7.31 Urgent whole spine MRI .................................................................................................. 14

7.4 Management .......................................................................................................................... 14

7.41 Analgesia .......................................................................................................................... 14

7.42 Steroids ............................................................................................................................. 14

7.43 Referral to MSCC Coordinating Team ............................................................................. 15

7.44 Surgery .............................................................................................................................. 15

7.45 Radiotherapy .................................................................................................................... 15

7.46 Chemotherapy .................................................................................................................. 15

7.47 Best supportive care (BSC) ................................................................................................ 15

7.48 Rehabilitation ................................................................................................................... 15

7.5 Outcome ................................................................................................................................. 15

8. Management of Cerebral Space Occupying Lesion (Brain metastases) .................................... 16

8.1 Introduction ............................................................................................................................ 16

8.2 Diagnosis and early suspicion ................................................................................................. 16

8.3 Management .......................................................................................................................... 16

8.4 General symptomatic measures ............................................................................................. 16

8.41 Cerebral oedema and raised intracranial pressure ......................................................... 16

8.42 Headache .......................................................................................................................... 17

8.43 Seizures ............................................................................................................................. 17

8.44 Nausea and vomiting ....................................................................................................... 17

8.45 Confusion, agitation or psychosis .................................................................................... 17

8.5 Specific treatment options ..................................................................................................... 17

8.51 Solitary Brain Metastases ................................................................................................. 17

8.52 Chemotherapy .................................................................................................................. 18

8.53 Radiotherapy .................................................................................................................... 18

8.6 Rehabilitation & Discharge Planning ..................................................................................... 18

8.7 Outcome ................................................................................................................................. 18

8.8 Symptoms and quality of life ................................................................................................. 18

8.9 Survival ................................................................................................................................... 18

8.10 Place of care ......................................................................................................................... 19

8.11 Follow-up .............................................................................................................................. 19

9. Management of Radiation Induced Dermatitis .......................................................................... 20

9.1 Introduction ............................................................................................................................ 20

9.11 Grading system and symptoms and signs on clinical examination .................................. 20

9.2 Investigations ......................................................................................................................... 20

9.3 Management .......................................................................................................................... 20

9.4 Outcome ................................................................................................................................. 21

10. Management of Radiation Induced Pneumonitis ..................................................................... 22

10.1 Introduction .......................................................................................................................... 22

10.11 Grading system and symptoms and signs on clinical examination ............................... 22

10.2 Symptoms include................................................................................................................. 22

10.3 Investigations........................................................................................................................ 22

10.4 Management ........................................................................................................................ 23

10.5 Outcome ............................................................................................................................... 23


11. Management of Acute Mucositis caused by Radiotherapy and/or Chemotherapy................ 24

11.1 Introduction .......................................................................................................................... 24

11.2 Grading system and symptoms and signs on clinical examination ...................................... 25

11.3 Investigations........................................................................................................................ 26

11.4 Management ........................................................................................................................ 26

11.41 Basic oral care ................................................................................................................. 26

11.42 Mouth washes with local analgesics, coating agents or oral rinses: ............................ 26

11.43 Pain management: ......................................................................................................... 27

11.44 Maintain adequate hydration and nutrition: ................................................................ 27

11.45 Prophylactic Radiologically inserted Gastrostomy (RIG) or Percutaneous Endoscopic Gastrostomy (PEG) .................................................................................................................... 27

11.46 Supra infection management: ....................................................................................... 28

11.5 Outcome ............................................................................................................................... 28

12. Management Chemotherapy and Radiotherapy Induced Diarrhoea ...................................... 29

12.1 Introduction .......................................................................................................................... 29

12.2 Evaluation of cancer treatment induced diarrhoea............................................................. 30

12.3 Management of cancer treatment-induced diarrhoea ........................................................ 30

12.4 Foods and medications to avoid in chemotherapy-induced diarrhoea ............................... 32

12.5 Treatment ............................................................................................................................. 32

12.6 Recommendations of an independent panel for management of diarrhoea in patients receiving the IFL regimen ............................................................................................................. 32

12.7 Octreotide ............................................................................................................................. 33

13. Management Chemotherapy and Radiotherapy Induced Nausea and Vomiting ................... 34

13.1 Introduction .......................................................................................................................... 34

13.11 High risk .......................................................................................................................... 35

13.12 Moderate risk ................................................................................................................. 35

13.13 Low risk ........................................................................................................................... 35

13.14 Minimal risk .................................................................................................................... 35

13.15 Anticipatory emesis ........................................................................................................ 36

13.16 High-dose chemotherapy ............................................................................................... 36

13.17 Poor emesis control ........................................................................................................ 36

13.2 Assessment of level of emetogenicity .................................................................................. 36

13.3 Emetogenic risks of chemotherapy ...................................................................................... 37

13.4 Table 1 .................................................................................................................................. 38

13.4 References ............................................................................................................................ 39

13.5 Emetic risk category of the radiation administered ............................................................ 40

13.51 High and Moderate Risk ................................................................................................ 40

13.52 Low and Minimal Risk .................................................................................................... 40

13.6 References ............................................................................................................................ 40

14. Management Algorithm for Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) in Oncology ........................................................................................................................ 41


1. Management of Malignant Ascites

1.1 Introduction Most often ascites results from non-malignant causes. Cancer accounts for less than 10% of cases. Some patients have two causes for ascites formation (e.g. cirrhosis plus peritoneal carcinomatosis). Ascites typically develops in the setting of recurrent and/or advanced cancer. Metastatic ovarian, breast and colorectal cancers are the commonest malignant causes.

1.2 Symptoms and Signs

• Abdominal pain due to a nerve invasion by the tumour, stretching of the liver capsule, or (in tense ascites) stretching of the abdominal wall.

• Shortness of breath. • Early satiety. • Bulging flanks with dullness to percussion.

1.3 Investigations Patient with suspected ascites should undergo imaging to confirm the ascites and to mark the site for aspiration. In known cases of malignancy, and where paracentesis is done to ease intra-abdominal pressure and relieve symptoms, there is no need for testing ascetic fluid. However if clinical situation demands then ascitic fluid should be sent for cell count (including differential), protein analysis and serum-to-ascites albumin gradient.

1.4 Management Therapeutic paracentesis is the mainstay of treatment. Frequency should be guided by the patient's symptoms (i.e. distension, shortness of breath, and early satiety). Large volumes of fluid (up to 21 litres) can be removed without fear of haemodynamic sequelae, including circulatory failure. Intravenous albumin infusion is generally not necessary. For recurrent ascites, a peritoneal port (pleurex drain) can be placed to facilitate repeated paracentesis. Diuretics are less likely to work in malignant ascites, but if considered appropriate spirinolactone (50-100 mg) or furosemide (40 mg) can be tried.

1.5 Outcome Outcome depends upon aetiology of cancer. Apart from ovarian cancer, out come is generally poor with an average life expectancy around 3 to 6 months. Therefore in majority of cases aim of the treatment is symptom control.


2. Management of Malignant Pleural Effusion 2.1 Introduction Malignant pleural effusions in patients with cancer are indicative of advanced disease with associated reduced life expectancy. The commonest causes of effusion are due to lung cancer and breast cancer. It’s important to determine the exact aetiology of each effusion as the best treatment options differ between tumour sites. The median survival with an effusion secondary to lung cancer is around 3 months and compared with >12 months for breast cancer associated effusions. These 2 sites make up at least 60% of all malignant effusions with an intermediate prognosis for other tumour sites. Mesothelioma associated effusions generally have a better prognosis than other forms of lung cancer. Where possible management should occur between Oncology and Chest Physicians and input from other specialities as required.

2.2 Symptoms and Signs The majority of pleural effusions present with progressively increasing breathlessness over a period of weeks to months. Up to 25% can be asymptomatic. Cough and chest pains may be present but are not often found.

2.21 Signs of effusion

• Decreased respiratory excursion on the effected side • Increase in respiratory rate • Dullness to percussion • Decreased breath sounds

The effusions may be of any size ranging from clinically undetectable to a complete whiteout. Generally the larger the effusion the more likely it is to be malignant. Increased respiratory rate, respiratory distress as demonstrated by respiratory failure and tracheal deviation away from the side of the effusion are indicative of and should be treated as a medical emergency.

2.3 Investigations

• Physical examination • Chest x-ray • Thoracic ultrasound • CT scanning

2.4 Management

2.41 Emergency presentations

Patients presenting with signs suggestive of mediastinal shift or respiratory failure should be treated at the time of presentation. Ideally thoracic ultrasound should be performed prior to a therapeutic aspiration of 1 litre of fluid. This should reduce symptoms to allow a more considered approach.


2.42 Non-emergency presentations

In patients with known malignancy who have small asymptomatic effusions intervention is not necessarily require other than radiological and clinical surveillance In other cases wherever possible the malignant cause of the effusion should be confirmed through cytological examination of the pleural fluid. The treatment of choice depends upon the likely prognosis for the patient. If the outlook is relatively good, i.e. as with most patients with breast cancer, the ideal treatment would be to drain the effusion completely and then to instil an agent to induce a chemical pleurodesis to prevent re-accumulation of the fluid. The method chosen to achieve this would depend upon local availability of services such as surgical approaches through a Video Assisted Thoracoscopic Surgery, medical thoracoscopy or small bore chest drain insertion. The ideal pleuradesing agent is TALC poudrage or TALC slurry depending upon local availability. Before this is contemplated ultrasound and / or cross sectional limiting should be performed to ensure that the lung is likely to re-inflate fully and is not entrapped. This approach is most suitable for patients with breast cancer and mesothelioma. In patients with a poor prognosis, i.e. <1 month, the best treatment is probably the simplest which would be merely a therapeutic aspiration. For those people with an intermediate prognosis then a discussion needs to occur between the chest physician, Oncologists and patient as to the most appropriate form of treatment. In some, this will be chest fluid drainage with an attempt at the pleurodesis or simple aspiration. An alternative choice would be to consider the placement of a long term pleural catheter. There are a number commercially available. This enables drainage to be performed in the community either by the patient or their carers. This is an increasingly popular choice.


3. Management of Pericardial Effusion 3.1 Introduction Accumulation of fluid within the pericardial sac leading to effusion can be a presenting symptom in the acute oncology patient. Pericardial tamponade due to malignant pericardial effusion (MPCE) accounts for at least 50% of all reported cases that require intervention. MPCE is frequently indicative of advanced incurable malignancy with a median survival of less than 6 months. Metastases from the lung or breast account for 75% of cases. MPCE is rarely the initial manifestation of extra cardiac malignancy with only a handful of such cases reported in the literature.


• Dyspnoea, cough • Chest pain worse on inspiration or lying flat relieved on sitting forward • Fever • Raised JVP with prominent x descent • Bronchial breathing at left base • Increased heart rate • Decreased blood pressure Signs of • Pulsus paradoxus tamponade • Increased JVP (Kussmaul’s sign: JVP rising with inspiration) • Muffled heart sounds

3.3 Investigations • ECG • CXR • Echocardiography

3.4 Management Symptomatic pericardial effusion and specifically cardiac tamponade needs urgent expert help. Refer to trust policies and refer to cardiology team or acute medical team to consider pericardiocentesis and further management as appropriate. Questions as to the appropriateness of treatment can be discussed with the patient and family members and the patient’s oncology consultant or on call oncologist.

3.5 Outcome Immediate short term relief can occur with pericardiocentesis. In the longer term balloon pericardotomy may be required if there are no further systemic treatments available for the malignancy in question. Radiotherapy can rarely be used.


4. Management of Lymphangitis Carcinomatosa 4.1 Introduction Lymphangitis carcinomatosa, more commonly abbreviated to lymphangitis, is characterised by the development of severe and constant breathlessness caused by the blockage of the lymphatic drainage of the lungs by hilar nodal involvement. The lungs become congested and stiffened with increased interstitial fluid resulting in a reduced capacity for transferring oxygen. Lymphangitis is common in patents with lung cancer but also occurs commonly in metastatic breast and gastrointestinal cancers.

4.2 Diagnosis There are no specific clinical features of lymphangitis though an unproductive cough and basal crackles may be present. Radiological changes are common on CXR and may be similar to those seen in acute left ventricular failure. Characteristic changes are often seen on CT scan.

4.3 Management The development of lymphangitis signals a poor prognosis in most cases and many patients are severely disabled by breathlessness. General, symptomatic measures are important.

4.4 Anti-cancer treatment Patients with cancers which are sensitive to chemotherapy or hormone therapy such as small cell lung cancer or breast cancer may improve with treatment but in many cases, the breathlessness is resistant to treatment and is often progressive. Radiotherapy to mediastinal or hilar nodes may occasionally be helpful.

4.5 Symptomatic treatment The general and pharmacological measures for the management of breathlessness outlined below are adapted from the ‘Yorkshire Cancer Network and Humber and Yorkshire Coast Cancer Network guide to symptom management in palliative care’.

4.6 Pharmacological treatment All drugs for symptomatic relief of dyspnoea are respiratory sedatives. When prescribed, their use should be monitored carefully. In the context of distressing dyspnoea in the terminal stages of illness the benefits usually outweigh the risks.


4.61 Opioids

Oral morphine (immediate release) 2.5mg 4 hourly. Gradually titrate dose upward according to response or until unacceptable side-effects occur. This can be converted to a long acting morphine preparation if effective. If already taking strong opioid for analgesia contact palliative care team for advice. 4.62 Benzodiazepines Lorazepam 0.5mg-1mg SL may give rapid relief during panic attacks. For longer-term management consider oral diazepam 2mg once at night or twice daily. Midazolam 2.5mg SC may benefit patients that cannot tolerate oral/sublingual route. These drugs can be continued in the terminal phase as a continuous subcutaneous infusion. Corticosteroids are often started in the hope of reducing pulmonary congestion but there is no evidence to support this practice. Steroids may give relief of breathlessness by a variety of mechanisms and a short trial is usually worthwhile, stopping after 7 days if there has been no benefit.

4.7 General symptomatic measures

• Dyspnoea is frightening to patient, family and staff. Reassurance and explanation are vital parts of the treatment whatever the cause.

• Modification of lifestyle, breathing retraining and relaxation may be beneficial if instituted early enough - consider referral to a physiotherapist.

• A table or hand-held fan directed onto the face often eases dyspnoea. • Good oral care is important if there is persistent mouth breathing. • Humidified oxygen may help acute dyspnoea but should be used alongside other

measures and its use reviewed regularly. • Long term oxygen therapy for chronic respiratory illness should only be instigated by

respiratory physicians. • Many patients requiring palliation for breathlessness will not benefit from oxygen

therapy. Measurement of oxygen saturation levels using a pulse oximeter may aid decision making in assessing whether or not oxygen is of benefit.


5. Management of Superior Vena Cava Obstruction 5.1 Introduction Most commonly seen in lung cancer. Consider lymphoma, particularly in young patients. Regard as an emergency as the patient’s condition may deteriorate rapidly.


• Swelling of the face and neck • Feeling of fullness in the head • Dyspnoea, worse on lying flat • Non-pusatile raised JVP • Dilated anterior chest wall veins

5.3 Investigations

• Discuss with radiologist regarding local policy • CXR • Chest CT

5.4 Management Vascular stenting is usual treatment of choice although radiotherapy or chemotherapy may be good alternatives. Chemotherapy may be treatment of choice in lymphoma and small cell lung cancer. The evidence for the use of steroids as a holding measure before definitive treatment is lacking. Where used, this should be of limited duration. Discussion with the local respiratory team and / or oncologist is recommended.

5.5 Recurrent superior vena cava obstruction Radiotherapy may be considered. Vascular stent may be replaced. Thrombolysis may be considered if a stent is blocked by thrombus.

5.6 Outcome Treatment often gives useful symptomatic relief. In untreatable SVCO, end of life measures are required.


6. Management of Hypercalcaemia 6.1 Introduction Hypercalcaemia affects approximately 10-20% of patients with advanced cancer. It’s most commonly seen in multiple myeloma, breast, renal and squamous carcinomas. Consider in unexplained nausea, vomiting or confusion. More commonly due to tumour secretion of parathyroid hormone related protein than to bone metastases. May develop insidiously.

6.2 Symptoms and signs

• Severity of symptoms is more related to the speed of rise of serum calcium rather than to absolute level.

• Non-specific early symptoms: lethargy, malaise, anorexia. • Common symptoms: nausea and confusion. • Other symptoms: constipation, thirst and dehydration. • Late features: drowsiness, fits and coma.

6.3 Investigations

• Corrected serum calcium • Urea and electrolytes

6.4 Management Treat if corrected calcium >2.8, symptomatic and clinically appropriate. Intravenous bisphosphonate e.g. Zoledronic acid 4mg. Choice depends on local guidelines and renal function. Pre and post dose rehydration with 0.9% normal saline tailored to the patient’s renal function, cardiovascular status and oral intake.

6.5 Outcome Initial episodes usually successfully treated as above. Patients may need regular bisphosphonates under oncology care to prevent recurrent episodes. Best treatment is that of underlying malignancy.


7. Malignant Spinal Cord Compression

7.1 Introduction Metastatic spinal cord compression (MSCC) is seen in 15% of all cancer patients and in up to half of these, it is the first presentation of their cancer. Breast, lung and prostate cancer account for more than 50% of all cases. MSCC is also seen in renal cell cancer, myeloma and in lymphoma amongst others. MSCC requires early recognition and prompt referral as restoration of neurological function is rarely possible for those who have lost it by the time they start treatment.

7.2 Symptoms and signs

• Pain is the presenting symptom in 90 to 95%; this can be localised or radicular. • Limb weakness. • Sensory disturbances. • Autonomic dysfunction. • Weakness / paraparesis / paraplegia. • Change in sensation below level of lesion (not always complete loss of sensation). • Reflexes – absent at level of lesion – increased below it. • Clonus. • Painless bladder distension. • Loss of anal tone.

7.3 Investigations

• The absence of signs does not exclude early spinal cord compression. • Investigations should be considered on the basis of history alone in at risk patients.

7.31 Urgent whole spine MRI Arranged by the admitting team and performed within 24 hours if MSCC is suspected. 7.4 Management 7.41 Analgesia As per the WHO analgesic ladder. 7.42 Steroids Dexamethasone 16mg stat intravenously, then 8mg orally (PO) twice a day (BID) or 4mg four times daily (QDS) if no contraindications. It should be accompanied with a proton pump inhibitor (PPI) cover. Steroid should start as soon as MSCC suspected.


7.43 Referral to MSCC Coordinating Team All cases to be referred following NEYHCA (Cancer) MSCC pathway. Please press control and click on the following link

http://www.hyccn.nhs.uk/NetworkGuidelinesAndPublications/mscc.htm It is the responsibility of the admitting team to urgently refer cases of MRI diagnosed MSCC with the aim of definitive treatment (if indicated) within 24 hours of diagnosis. 7.44 Surgery All cases of confirmed MSCC should be discussed with the neurosurgical team on call at HRI. Venous thrombosis risk evaluation and prophylaxis 7.45 Radiotherapy If surgery is not recommended then urgent referral to oncology is indicated. Radiotherapy is useful for pain control as well as MSCC management. 7.46 Chemotherapy In selected cases like haematological malignancies, small cell lung cancer and germ cell tumours, chemotherapy could be the preferred first line of management. 7.47 Best supportive care (BSC) BSC should be considered for patients with poor performance status and / or for those who have been totally paraplegic for more than 24 hours. 7.48 Rehabilitation Physiotherapist and occupational therapist will start the rehabilitation program at an early stage as indicated.

7.5 Outcome

• Early diagnosis, referral and treatment are the major determining factors for a successful out come in the management of MSCC.

• Patients whose mobility has been affected will require a prolonged period of rehabilitation and home adaptations prior to discharge.

• Prognosis is greatly affected by performance status, ambulatory status and the background malignant condition treatment options available.


8. Management of Cerebral Space Occupying Lesion (Brain metastases) 8.1 Introduction Metastases to the brain are a common problem in oncology, affecting 17–25% of the cancer population. They are common in lung cancer affecting 26% of patients with this disease, breast cancer (16%), renal cancer (13%), colorectal carcinoma (5%) and in melanoma (4%). In the majority of patients, the diagnosis of cerebral metastases carries a poor prognosis.

8.2 Diagnosis and early suspicion Brain metastases frequently masquerade as a stroke or less commonly as seizures in patients not previously known to have a diagnosis of cancer, the correct diagnosis being made at CT or MRI scan. Brain metastases should be considered in all those known to have cancer presenting with any of the symptoms listed.

• Headache • Nausea / Vomiting • Focal weakness / hemiparesis • Confusion • Unsteadiness • Seizures • Visual disturbance • Dysphasia

8.3 Management In many patients, the presence of cerebral metastases is a component of widely disseminated disease and is often associated with a poor performance status and prognosis. The focus of management for this group is general symptomatic care and consideration of psychosocial needs. For a selected group of patients with a better prognosis, active treatment may be appropriate.

8.4 General symptomatic measures 8.41 Cerebral oedema and raised intracranial pressure Acute treatment is with steroids: dexamethasone 8mg initially which should only be given parenterally when there is concern about absorption e.g. in the presence of vomiting. This should be followed by dexamethasone 16mg daily in two divided doses. Ideally the second dose should not be given after 2pm to avoid night time wakefulness and agitation though this should not preclude emergency administration of the first day’s dose. Intravenous mannitol may rarely be needed to reduce the intracranial pressure in a patient whose condition is worsening rapidly. Patients on high dose steroids should be observed for the development of glycosuria.


8.42 Headache Headache usually responds to steroids but regular paracetamol with the addition of codeine phosphate may be helpful and occasionally strong opioids may be required. 8.43 Seizures Once intracranial pressure is reduced, seizures may subside but some patients require regular anticonvulsant medication. The terminally ill patient with cerebral metastases and uncontrolled fitting may require parenteral benzodiazepines e.g. midazolam by continuous subcutaneous infusion. 8.44 Nausea and vomiting This usually responds to measures which reduce intracranial pressure, but antiemetics e.g. cyclizine or haloperidol may be required and may need to be given parenterally at first. 8.45 Confusion, agitation or psychosis The introduction of steroids may reverse acute problems but occasionally sedation may be required until the steroids take effect or as part of the management of terminal agitation.

8.5 Specific treatment options 8.51 Solitary Brain Metastases Surgical resection or stereotactic radiosurgery (SRS) are both used widely for the treatment of patients with an MRI-proven solitary metastasis who have limited extra-cranial disease and both a good prognosis and performance status. SRS uses finely focused beams of radiation and image guidance to treat the metastasis with a small margin to a high dose and is available in the UK in several larger radiotherapy centres. There has been no head-to-head comparison of surgery and SRS so the choice depends on local expertise, fitness for surgery, the size and site of the metastasis and patient choice {Fuentes R, 2006 #44}. The addition of whole brain radiotherapy to either of these local treatments seems to decrease the risk of relapse in the brain but does not impact on overall survival {Suh JH, 2010 #45}. Surgical resection may be more appropriate than SRS where there is no known primary cancer and the differential diagnosis lies between a primary brain tumour and a solitary metastasis or when the metastasis is too large for SRS. Surgery also has a role when raised intracranial pressure causes severe symptoms, especially with posterior fossa lesions. The multidisciplinary team is vital in the management of solitary brain metastases and cases which may be appropriate for surgery should be discussed at the neuro-oncology multidisciplinary team meeting. MDT Lead CNSs MDT Coordinator Mr S Achawal Louise Baker Joanne Ward Sec: Lesley Hart Lynne Gill Tel: 01482 607841 Tel HRI: 01482 607877 Tel HRI: 01482 607831 Fax: 01482 607892 Urgent referral / 2WW fax number:

01482 675505


8.52 Chemotherapy Systemic chemotherapy is useful for cancers which are chemosensitive, such as small-cell lung cancer and germ cell tumours and may also be useful in patients with breast cancer. Chemotherapy is usually followed by radiotherapy. 8.53 Radiotherapy Radiotherapy to the whole brain is commonly used and is usually given over 2–5 days. Steroids are continued throughout the treatment but are tailed off once it is complete, at a rate determined by symptoms though it is not often possible to stop steroids completely. Good response rates have often been quoted but studies using patient-rated scales suggest that benefit may often be outweighed by side effects (Box 1) {Bezjak A, 2002 #46} {Gerrard GE, 2003 #47}. For the patient with a poor performance status and poor prognosis, treatment with steroids and general supportive measures may be the best option.

Box 1 Side effects of whole brain radiotherapy

Acute Late (>6 months after completion of treatment)

Temporary alopecia Difficulties with memory and concentration

Headache Deterioration on neurocognitive testing

Nausea Persistent alopecia

Redness and soreness of the skin

Tiredness and sleepiness

8.6 Rehabilitation & Discharge Planning Many patients with brain metastases have a dramatic change in their functional ability, independence and personality. Many of their rehabilitation needs are similar to those outlined for patients with MSCC. In addition, some patients may need speech therapy and where appropriate, route of nutrition will need to be considered in those who have difficulty swallowing. There is a need for psychological support for both patient and carers.

8.7 Outcome

8.8 Symptoms and quality of life Both brain metastases and their treatment cause neurological symptoms and impair quality of life. A prospective study found that one month following whole brain radiotherapy, one fifth of 75 patients with brain metastases from a variety of primary cancers reported an improvement or resolution of their neurological symptoms and a similar number were stable. The rest had progressive symptoms or had died {Bezjak A, 2002 #46}. The challenge is to identify patients who are likely to benefit from treatment, concentrating on end of life care and symptom control for those who are unlikely to gain from intervention.

8.9 Survival The survival of patients with cerebral metastases is usually short. Performance status is the strongest predictor of survival although patients with non-small cell lung cancer have a particularly poor prognosis with a median survival of 2-3 months. Box 2 summarises the factors influencing survival.


Box 2 Factors affecting survival in patients with brain metastases

Factors that improve survival Solitary metastasis Long disease-free interval prior to relapse Primary site breast

Factors that reduce survival Poor performance status Extracranial sites of metastatic disease Primary site non-small cell lung cancer Meningeal disease

8.10 Place of care Many patients will be unable to be cared for at home because of loss of independence in activities of daily living, nursing needs and cognitive impairment. Changes in cognitive function in particular make care at home problematic and distressing to relatives.

8.11 Follow-up Symptomatic progression of brain metastases is common and is often accompanied by progressive extracranial disease. Close follow-up should be arranged in the community where care is usually centred for those without further anticancer treatment options.


9. Management of Radiation Induced Dermatitis

9.1 Introduction Radiation dermatitis is a side effect of external beam radiation. It occurs on the skin within radiation portals. It is a complex process of direct tissue injury and inflammatory cell recruitment, involving damage to epidermal basal cells, endothelial cells and vascular components and a reduction in Langerhans cells. The risk of developing this complication depends on the dose of the radiation deposited and the surface of the skin. Radiation induced acute dermatitis usually begins in 3rd or 4th week of radiotherapy, when standard fractionation is used, it aggravates towards the end of the treatment and gradually subsides once irradiation finishes. In most patients, the severity of radiation dermatitis is mild to moderate. The more severe skin reaction is usually present when radiotherapy is used to treat head and neck, anal or skin carcinomas. The use of concurrent chemotherapy or anti EGFR antibodies with RT shortens the onset, exacerbates the severity and prolongs the duration of the radiation dermatitis. 9.11 Grading system and symptoms and signs on clinical examination Common Terminology Criteria for Adverse Events (CTCAE v3.0)

Adverse Event

1 2 3 4 5

Rash: Dermatitis associated with radiation

Faint erythema or dry desquamation

Moderate to brisk erythema; patchy moist desquamation, mostly confined to skin folds and creases; moderate edema

Moist desquamation Other than skin folds and creases; bleeding induced by minor trauma or abrasion

Skin necrosis or ulceration of full thickness dermis; spontaneous bleeding from involved site

Death

On examination radiation dermatitis generally manifests within a few weeks after the start of radiotherapy. Its onset varies depending on the radiation dose intensity and the normal tissue sensitivity of individuals. As the cumulative dose of radiation increases, the transient erythema occurring during the first weeks of radiotherapy may evolve into the more persistent erythema to dry or even moist desquamation.

9.2 Investigations Usually there is no need for further investigations unless very severe skin reaction when swab for bacteriology may be of value.

9.3 Management The treatment strategy for the management of radiation dermatitis is based on symptoms control as there is no treatment proven to be effective. Topical treatment is the mainstay therapy for radiation dermatitis.


Patients should be encouraged to maintain good standards of skin hygiene. The irradiated area should be kept clean to minimise the risk of infection. Patients should

• Be provided with written and verbal information detailing skin care instructions. • Wash the area daily with a gentle cleanser, the use of a pH-neutral synthetic detergent

or mild soap is recommended. • Avoid rubbing the area and use a soft clean towel. • Avoid sun exposure wherever possible (soft clothing to cover the area and/or the use of

mineral sun blocks). • Avoid the use of skin irritants, such as perfumes or alcohol-based lotions. Deodorants

may continue to be used unless these are found to irritate the skin. • Avoid the use of paraffin or petroleum based creams and use aqueous cream.

In Grade 1 radiation dermatitis topical moisturisers should be used (e.g. aqueous cream) which should not be applied shortly before radiation treatment as they can cause a bolus effect, thereby artificially increasing the radiation dose to the epidermis. It is important to instruct patients to gently clean and dry the skin in the radiation field before each radiation session. In Grade 2 and 3 radiation dermatitis the following topical treatments are used

• Hydrogel application (e.g. Intrasite Gel) or hydrophilic dressing • Topical steroids (e.g. hydrocortisone 1% cream) • Silver Sulfadiazine 1% Cream (should be applied after radiotherapy)

The choice which of these topical treatments is used is based on patient preference and ability of regular use. Where skin infection is suspected topical antibiotics should be considered based on culture and sensitivity evaluation to provide patient with targeted evidence-based antimicrobial therapy. In Grade 4 dermatitis irradiation should be discontinued, but this decision should be only taken by the clinical oncology consultant. Wound specialist consultation is mandatory to select the appropriate dressing. Suprainfection should be treated with empirical systemic antimicrobial therapy usually with broad spectrum penicillin derivates or tetracycline. Culture and sensitivity evaluation is recommended when feasible to provide patient with targeted evidence-based antibiotic therapy. Adequate pain management according to the WHO ladder is necessary in all grades of radiation dermatitis.

9.4 Outcome Radiation dermatitis in the vast majority of cases is a reversible process and usually resolves with appropriate treatment following completion of the irradiation even when it was Grade 4.


10. Management of Radiation Induced Pneumonitis

10.1 Introduction Radiation pneumonitis is an inflammation of the lung tissue due to irradiation. This treatment toxicity occurs in 5-15% of patients having radiotherapy for lung cancer with radical intend. It can also result from radiation to the chest for other cancers; oesophageal, breast, lymphomas etc usually with lower incidence and severity compare lung primary. Radiation pneumonitis typically occurs between 1 and 3 months after completing radiation therapy with range of 2 weeks to 6 months. The risk of developing this complication depends on the dose of the radiation used and the volume of the lung tissue where high dose was delivered. It is more common if chemotherapy is given at the same time as radiotherapy, and is more likely to occur when there are pre-existing lung diseases, such as COPD. 10.11 Grading system and symptoms and signs on clinical examination Acute toxicity Common Terminology Criteria for Adverse Events (CTCAE v4.0).

Adverse Event

1 2 3 4 5

Pneumonitis Asymptomatic; clinical or diagnostic observations only; intervention not indicated

Symptomatic; medical intervention indicated; limiting instrumental ADL

Severe symptoms; limiting self care ADL; oxygen indicated

Life-threatening respiratory compromise; urgent intervention indicated (e.g., tracheotomy or intubation)

Death

Activities of Daily Living (ADL). *Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc. **Self care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden.

10.2 Symptoms include

• Shortness of breath especially on exertion • Persistent non productive cough • Chest pain especially that which worsens with breathing and low-grade fever

10.3 Investigations

• FBC, BCP • Oxygen saturation • Chest X-ray


10.4 Management Pulmonary embolism, infection, COPD exacerbation and tumour progression must be ruled out as these conditions can present with the same symptoms or coexist with radiation pneumonitis. For G1 observation only is recommended. The main treatment in grade 2 or higher radiation pneumonitis is high dose of corticosteroids; 60 mg/day of prednisolone orally in 1-4 divided doses. The other corticosteroids (e.g. dexamethasone) can be used in the equivalent doses. The initial iv administration of corticosteroids is recommended when severe respiratory distress is present precluding the oral administration. The high dose should be maintained until symptoms improvement with slow tapering afterwards. Prophylactic PPI (e.g. lansoprazole 30 mg OD) should be used to avoid gastrointestinal complications. Cough suppressants: Codeine 15-30 mg every 4-6 hours when severe cough. Pain killers and antipyrexials: Paracetamol 500-1000mg QDS. For G3 or higher radiation pneumonitis administration of oxygen is indicated and should be used according to local hospital guidelines. Respiratory failure in G4 should be treated according to local hospital guidelines. Coexisting pulmonary embolism, infection, COPD exacerbation or other cardiopulmonary illnesses should be treated according to local hospital guidelines.

10.5 Outcome Radiation induced pneumonitis in the majority of cases is reversible process and usually resolves with the treatment. If radiation pneumonitis persists, it can lead to post-radiotherapy lung fibrosis.


11. Management of Acute Mucositis caused by Radiotherapy and/or Chemotherapy 11.1 Introduction Mucositis is an acute injury to the mucosal lining of the head and neck region associated with cancer treatment (radiotherapy and/or chemotherapy). Radiotherapy and chemotherapy affect the mucosa directly through the toxic effects on rapidly dividing epithelial stem cells and lead to the interruption of the integrity of the mucosal barrier. Oral mucositis affects on average 35% to 40% of patients receiving cytotoxic chemotherapy. Cytotoxic drugs most commonly associated with mucositis are: Bleomycin, Cytarabine, Doxorubicin, Etoposide (high dose), Bolus 5-FU, Methotrexate (particularly high-dose). (See table 1 below for chemotherapy agents associated with mucositis) Chemotherapy-induced mucositis is typically less severe and of shorter duration (3-12 days) than that associated with RT. Table 1 Chemotherapy agents associated with mucositis

Category Specific Drugs

Alkylating agents

Busulfan Carmustine

Cyclophosphamide Dacarbazine Ifosfamide Lomustine Melphalan Thiotepa

Anthracyclines

Daunorubicin Doxorubicin Idarubicin Epirubicin

Mitoxantrone

Antimetabolites

Capecitabine Cytarabine Fluorouracil Fludarabine Gemcitabine

Hydroxcarbamide Methotexate

6-Mercaptopurine Pemetrexed

Antitumour antibiotics

Dactinomycin Bleomycin Mitomycin

Platinum Carboplatin Cisplatin


Taxanes Docetaxel Paclitaxel

Topoisomerase inhibitors

Etoposide Irinotecan Topotecan

Plant alkaloid

Vinblastine Vincristine Vindesine vinorelbine

Other antineoplastic

Estramustine Mitotane

Procarbazine

Radiation induced acute mucositis usually begins in 3rd or 4th week of radiotherapy when standard fractionation is used; it aggravates towards the end of the treatment and gradually subsides once radiation finishes. The severity of radiation induced mucositis is dose dependent and can last between 3-12 weeks. The use of concurrent chemotherapy with RT shortens the onset, exacerbates the severity and prolongs the duration of mucositis. When palliative radiotherapy is used mucositis is usually less severe and begins after completion of the course of irradiation.

11.2 Grading system and symptoms and signs on clinical examination Acute toxicity Common Terminology Criteria for Adverse Events (CTCAE v4.0)

Adverse Event

1 2 3 4 5

Mucositis oral

Asymptomatic or mild symptoms; intervention not indicated

Moderate pain; not interfering with oral intake; modified diet indicated

Severe pain; interfering with oral intake

Life-threatening consequences; urgent intervention indicated

Death

Pharyngeal mucositis

Endoscopic findings only; minimal symptoms with normal oral intake; mild pain but analgesics not indicated

Moderate pain and analgesics indicated; altered oral intake; limiting instrumental ADL

Severe pain; unable to adequately aliment or hydrate orally; limiting self-care ADL

Life-threatening consequences; urgent intervention indicated

Death

Activities of Daily Living (ADL) *Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc. **Self care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bed Symptoms include “mouth and throat sores”; difficulty swallowing; pain; lost or altered taste (dysgeusia); excessive secretions that may lead to gagging, nausea, and vomiting;


loss of appetite; fatigue; weight loss; and aspiration excessive and viscid mucus in the mouth and throat at later stage. On examination mild erythema is usually present at the onset of mucositis and is subsequently followed by patchy mucositis which may produce an inflammatory serosanguinitis discharge and later confluent fibrinous mucositis. Ulceration, haemorrhage or necrosis is typical for grade 4 mucositis. This could be complicated by oral candidiasis and HSV infections.

11.3 Investigations Regular weight check with BMI calculation FBC and BCP

11.4 Management The treatment strategy in management of acute mucositis caused by radiotherapy and/or chemotherapy is based on symptoms control as there is no proven causative treatment effective in management of this toxicity. It is recommended to focus on following groups of symptomatic management:

11.41 Basic oral care

• Good Oral Hygiene is highly recommended • Pre-treatment dental assessment with extractions when required is mandatory for

all patients having radical radiotherapy when high dose is delivered to oral cavity and/or oropharynx. Frequent rinsing with bland solutions such as normal saline with sodium bicarbonate (1 L water with 1/2 teaspoon baking soda and 1/2 teaspoon salt) and use of soft toothbrush.

• The oral cavity should be rinsed and wiped after meals, and dentures cleaned and brushed often to remove plaque. Rinsing with artificial saliva may lessen the duration and severity of mucositis.

• Diet should be limited to foods that do not require significant chewing; acidic, salty, or dry foods should be avoided. If the patient is unable to swallow foods or liquids, parenteral fluid and/or nutritional support may be needed.

11.42 Mouth washes with local analgesics, coating agents or oral rinses:

Barrier

Gelclair Mucilage Sucralfate MuGard Local Anaesthetics /Analgesic

Difflam (Benzydamine hydrochloride) Prophylaxis in high risk RT patients and transplant patients

Caphosol Prophylaxis in chemotherapy patients

Corsodyl (chlorhexidine)


Artifical saliva/biotene

Glandosane

11.43 Pain management:

Adequate analgesia is extremely important in the management of mucositis. Treatment should be arranged according to WHO ladder and pain killers should be given in liquid or transdermal form as swallowing is usually severely altered. Initial Paracetamol soluble tablets 500-1000mg QDS at G1 is usually followed by soluble (codeine and paracetamol) 8/500 or 30/500 1-2 tablets QDS when G2. At G3 and G4 usually strong opioid analgesia is required. Liquid modified release morphine 12 hourly preparations or fentanyl patches in increasing doses are used with the choice of them based on the patient’s preference and tolerance. Oral solution of Oramorph is used for breakthrough pain.

11.44 Maintain adequate hydration and nutrition:

All patients having radical radiotherapy should be routinely provided with dietician support upfront right from the beginning of irradiation. For palliative radiotherapy and chemotherapy patients this should be provided on an as needed basis.

11.45 Prophylactic Radiologically inserted Gastrostomy (RIG) or Percutaneous Endoscopic Gastrostomy (PEG)

Prophylactic RIG (radiologically inserted gastrostomy) or PEG (percutaneous endoscopic gastrostomy) is a gastrostomy that is placed in anticipation of problems expected in maintaining adequate and safe oral nutritional intake during and after the radiotherapy treatment for head and neck patients. A patient having a prophylactic gastrostomy may be managing adequate oral nutrition at the time of placement. Prophylactic RIG or PEG prior to radiotherapy should routinely be requested for all patients planned for radical chemo-radiotherapy to bilateral neck. For other patients planned for radical radiotherapy to large volume of head and neck e.g. nearly total mucosal irradiation and/or planned for radical radiotherapy to large volume of oral cavity and/or oropharynx gastrostomy request is to be based on individual case discussion between assigned clinical oncology consultant and the rest of the treatment head and neck team. Prophylactic feeding tube placement through speech valve fistula for post laryngectomy patients should be considered as alternative to RIG or PEG. The remaining group of patients having radiotherapy for head and neck cancer when prophylactic gastrostomy is not indicated or refused by patient or having chemotherapy related mucositis are to be managed as follows:

• Diet modification e.g. soft food, semi liquid food etc. along with adequate analgesia.

• Oral nutritional supplements. NG (nasogastric) tube placement and feeding - when 1 and 2 fail to maintain adequate and safe oral nutrition and hydration.


If acute problems with dehydration IV fluids with serum electrolyte correction to be considered. If there is prolonged use of NG tube post treatment, use of therapeutic RIG or PEG to be considered.

11.46 Supra infection management:

Patients with such complication should be treated with empiric antimicrobial therapy usually with fluconazole 50 mg OD in case of fungal infection or penicillin derivates in case of bacterial infection. Culture and sensitivity evaluation is recommended when feasible to provide patient with targeted evidence-based antibiotic therapy.

11.5 Outcome Treatment usually gives useful symptomatic relief and enables continuation of radiotherapy and/or chemotherapy to prescribed doses. When radiation induced mucositis riches G4 discontinuation of radiotherapy is recommended, however this decision should be only taken by assigned clinical oncology consultant. When G3 or G4 chemotherapy induced mucositis dose reduction and/or delay of next cycle should be considered according to local chemotherapy guidelines.


12. Management Chemotherapy and Radiotherapy Induced Diarrhoea

12.1 Introduction Chemotherapy-induced diarrhoea (CID) is a common side effect of cancer treatment and can cause significant morbidity and mortality. Diarrhoea is frequently severe enough to require a dose reduction of, a delay in, or a discontinuation of chemotherapy. Diarrhoea-associated mortality has been reported to be as high as 3.5% in clinical trials of irinotecan and bolus 5-fluorouracil in colorectal cancer. The frequency of CID and its impact on patient management are frequently under-recognized in clinical practice. Estimates of the incidence of diarrhoea suggest that 40% of patients with advanced cancer experience acute or persistent diarrhoea that may range from troublesome (grade 1) to lethal (grade 5), based on National Cancer Institute–Common Toxicity Criteria (NCI–CTC) [table 1]. Classification Chemotherapy induced diarrhoea is graded using the NCI criteria (Table 1) Table 1 NCI criteria for assessment of chemotherapy-induced diarrhoea

Toxicity Grade

Criteria

1 Increase of <4 stools daily over baseline Mild increase in colostomy output as compared with baseline

2 Increase of 4–6 stools daily over baseline Intravenous fluids indicated <24 hours Moderate increase in colostomy output compared with baseline Not interfering with activities of daily living

3 Increase of ≥7 stools daily over baseline Incontinence; intravenous fluids >24 hours Hospitalization Severe increase in colostomy output compared with baseline Interfering with activities of daily living

4 Life-threatening consequences (for example, hemodynamic collapse)

5 Death The common drugs causing diarrhoea include fluoropyrimidines (particularly 5-fluorouracil [5-FU] and capecitabine) and irinotecan. Some others include Pemetrexed, Cabazitaxel, Bortezomib, Vorinostat, small molecule EGFR inhibitors like Erlotinib, Gefitinib, Sorafenib, Sunitinib, Imatinib, Lapatinib, Everolimus, Temsirolimus, Cetuximab and Panitumumab (anti EGFR monoclonal antibodies)


Chemotherapy (5FU) causes acute damage to the intestinal mucosa, leading to loss of epithelium [1]. 5-FU induces mitotic arrest of crypt cells, leading to an increase in the ratio of immature secretory crypt cells to mature villous enterocytes [2]. The increased volume of fluid that leaves the small bowel exceeds the absorptive capacity of the colon, leading to clinically significant diarrhoea 1.Milles, SS, Muggia, AL, Spiro, HM. Colonic histological changes induced by 5-fluorouracil. Gastroenterology 1962; 43:391 2. Ikuno N, Soda H, Watanabe M, Oka M. Irinotecan (CPT-11) and characteristic mucosal changes in the mouse ileum and cecum. J Natl Cancer Inst 1995; 87:1876.

12.2 Evaluation of cancer treatment induced diarrhoea

Obtain history of onset and duration of diarrhoea Describe number of stools and stool composition (eg, watery, blood in stool, nocturnal) Assess patient for fever, dizziness, abdominal pain/cramping, or weakness (ie, rule out risk for sepsis, bowel obstruction, dehydration) Medications profile (ie, to identify diarrhoea-inducing agents) Dietary profile (ie, to identify diarrhoea-enhancing foods) Continue to Management of Cancer Treatment-Induced Diarrhoea Algorithm

12.3 Management of cancer treatment-induced diarrhoea The recommendations of a consensus conference on the management of CID were published in 1998 and updated in 2004. Guidelines for evaluation and management of patients with CID are presented in the following figures (table and figure) Benson AB 3rd, Ajani JA, Catalano RB, et al. Recommended guidelines for the treatment of cancer treatment-induced diarrhoea. J Clin Oncol 2004; 22:2918.]. The tempo and specific nature of treatment is guided by the classification of the symptom constellation as complicated or uncomplicated.

Uncomplicated patients may be managed conservatively in the outpatient setting (at least initially), while those with severe diarrhoea or a potentially exacerbating condition (eg, abdominal cramping, nausea, vomiting, fever, sepsis, neutropenia or bleeding) should be admitted to the hospital and treated aggressively with octreotide, intravenous fluids, antibiotics, and a diagnostic workup.


CTC: Common Toxicity Criteria; RT: radiotherapy; IV: intravenous; SC subcutaneous; tid: three times per day; CBC: complete blood count; CID: chemotherapy-induced diarrhoea.

* For RT-induced cases and select patients with CID, consider intensive outpatient management, unless the patient has sepsis, fever, or neutropenia.


12.4 Foods and medications to avoid in chemotherapy-induced diarrhoea

Food products

Milk and dairy products (since lactase deficiency may be induced by mucosal injury) Spicy foods Alcohol Caffeine-containing products High fiber and high fat foods Some fruit juices (eg, prune juice, orange juice) Medications

Bulk laxatives Stool softeners Promotility drugs (eg, metoclopramide)

12.5 Treatment The treatment of CID includes non-pharmacologic and pharmacologic interventions to slow the diarrhoea and careful serial evaluation to rule out significant volume depletion or co morbidities that would require targeted intervention or hospitalization. Initial non-pharmacologic measures include avoidance of foods that would aggravate the diarrhoea (table above) and aggressive oral rehydration with fluids that contain water, salt, and sugar (since glucose promotes intestinal sodium absorption) such as broth or Gatorade. These principles are similar to those used for infectious diarrhoea. The mainstay of the drug therapy of CID is the opiates. Loperamide (Imodium) and co-phenotrope 2.5/0.025 (Lomotil) are the most commonly used. The standard dose of loperamide is an initial 4 mg dose followed by 2 mg every four hours or after every formed stool. This regimen is only moderately effective in CID and a more aggressive regimen (4 mg initially, then 2 mg every two hours or 4 mg every four hours until diarrhoea-free for 12 hours) is often required, particularly for irinotecan-induced diarrhoea (table below)

12.6 Recommendations of an independent panel for management of diarrhoea in patients receiving the IFL regimen Clinical presentation Intervention Diarrhoea, any grade Oral loperamide (2 mg every 2 hours) until

diarrhoea-free for ≥12 hours Diarrhoea persists on loperamide >24 hours Oral fluoroquinolone x 7 days Diarrhoea persists on loperamide >48 hours Stop loperamide; hospitalize the patient,

administer IV fluids Neutropenic (ANC <500 microL), even in the absence of fever or diarrhoea

Oral fluoroquinolone, continue until resolution of neutropenia

Fever with persistent diarrhoea, even in absence of neutropenia

Oral fluoroquinolone, continue until resolution of fever and diarrhoea


12.7 Octreotide A synthetic long-acting somatostatin analog, acts via several mechanisms: decreased secretion of a number of hormones, such as vasoactive intestinal peptide (VIP); prolongation of intestinal transit time; and reduced secretion and increased absorption of fluid and electrolytes. Octreotide is also beneficial in patients with CID from fluoropyrimidines, irinotecan, and 5-FU-based chemo radiotherapy although the optimal dose has not been determined.

The recommended starting dose of octreotideis 100 to 150 microgram subcutaneously, three times a day; however, several reports suggest that higher doses (500 microgram) may be more effective

The side effects of octreotide are generally mild, including bloating, cramping, flatulence and fat malabsorption. Hypersensitivity-like reactions and hypoglycaemia can occur at higher doses.


13. Management Chemotherapy and Radiotherapy Induced Nausea and Vomiting

13.1 Introduction Nausea and Vomiting are among the most feared and distressing adverse effects of chemotherapy from a patient’s standpoint.(1-3) Substantial progress has been made in improving the control of chemotherapy-induced nausea and vomiting (CINV) due in large part to the introduction of selective type-three 5-hydroxytryptamine (5-HT3) receptor antagonists approximately 13 years ago (4). Nevertheless, CINV remains sub optimally controlled for a significant number of cancer patients receiving chemotherapy.

The following distinct types of CINV have been defined, with important implications for both prevention and management:

• Acute emesis, which most commonly begins within one to two hours of chemotherapy and usually peaks in the first four to six hours (<1 day post chemo)

• Delayed emesis, occurring more than 24 hours after chemotherapy (1 - 7 days post chemotherapy)

• Anticipatory emesis, occurring prior to treatment as a conditioned response in patients who have developed significant nausea and vomiting during previous cycles of chemotherapy.

• Breakthrough emesis refers to vomiting despite pre-treatment and requires rescue with additional antiemetics.

• Refractory- continued emesis in subsequent treatment cycles when prophylaxis and rescue antiemetics have failed in previous cycles

The objective of antiemetic therapy is the complete prevention of CINV, and this should be achievable in the majority of patients receiving chemotherapy, even with highly emetogenic agents. The three categories of drugs with the highest therapeutic index for the management CINV include Corticosteroids, type three 5-hydroxytryptamine (5-HT3) receptor antagonists, and the neurokinin-1 (NK1) receptor antagonist aprepitant.

The management of CINV has been greatly facilitated by the development of classification schemes that reflect the likelihood of emesis developing following treatment with a particular agent. A 1997 classification scheme gained broad acceptance and was utilized as the basis for treatment recommendations by guideline panels. [5]. A modification of this schema was proposed at the 2004 Perugia Antiemetic Consensus Guideline meeting [6].


Chemotherapy agents were divided into four categories

• High — >90 percent risk of emesis • Moderate — >30 to 90 percent risk of emesis • Low — 10 to 30 percent risk of emesis • Minimal — <10 percent risk of emesis

This drug classification schema is utilized in both the updated antiemetic guidelines of the Multinational Association of Supportive Care in Cancer (MASCC) and the American Society of Clinical Oncology. [7].

The following are the general recommendations for the antiemetic use. (See Table 1 below)

13.11 High risk

For patients receiving cisplatin-based chemotherapy or another agent with high emetogenic risk, therapy with a combination of a 5-HT3 receptor antagonist, dexamethasone and aprepitent (Grade1A) is recommended. To prevent delayed emesis, maintenance therapy with a combination of dexamethasone and aprepitant (Grade 1A) is recommended. Anthracycline plus cyclophosphamide - For patients receiving chemotherapy with cyclophosphamide plus an anthracycline, antiemetic therapy with a combination of a 5-HT3 receptor antagonist, dexamethasone and aprepitant (Grade 1A) is recommended. After day one, recommend maintenance treatment with aprepitant as a single agent to prevent delayed emesis (Grade 1B).

13.12 Moderate risk

For patients receiving moderately emetogenic chemotherapy other than the combination of anthracycline plus cyclophosphamide, recommend the combination of a 5-HT3 receptor antagonist plus dexamethasone (Grade 1A).

• To prevent delayed emesis in this population, suggest single agent treatment with dexamethasone (Grade 2B).

• Treatment with a 5-HT3 receptor antagonist alone is a reasonable alternative.

13.13 Low risk

For patients receiving low emetic risk agents, treatment with dexamethasone (8 mg) as a single agent (Grade 2C) is suggested. This patient population generally does not require prophylaxis against delayed emesis.

13.14 Minimal risk

For patients receiving chemotherapy agents with minimal risk of causing emesis), we suggest that antiemetic therapy not be routinely administered for either acute or delayed CINV (Grade 2B).


13.15 Anticipatory emesis

The primary approach to the prevention of anticipatory emesis is the prevention of CINV beginning with the initial cycles of chemotherapy. For patients who do develop anticipatory emesis, suggest behavioural therapy or benzodiazepines (Grade 2B).

13.16 High-dose chemotherapy

Patients receiving high-dose chemotherapy are at increased risk for the development of CINV. A combination of dexamethasone, a 5-HT3 receptor antagonist, and aprepitant is suggested (Grade 2B).

13.17 Poor emesis control

For patients who do not achieve adequate control of CINV with their initial antiemetic regimen, the patient's management should be reviewed to ensure that there are no other factors responsible for continued emesis and that adequate antiemetic therapy actually was administered for the given chemotherapy regimen. If CINV remains an issue, the addition or substitution of a second line agent or changing from one 5-HT3 receptor antagonist to another may be useful.

13.2 Assessment of level of emetogenicity The following flow diagram may help to prescribe and adjust the antiemetic requirements.

Approach to the prevention and treatment of chemotherapy-induced emesis


13.3 Emetogenic risks of chemotherapy Chemotherapeutic agents carry varying emetogenic potentials. The following table highlights the risk of the most commonly used chemotherapy drugs. If a multi-drug regimen is being used, the anti-emetics used should be tailored to the most emetogenic component of the regimen.

FREQUENCEY RISK OF EMESIS High (>90%) Moderate (30-90%) Low (10-30%) Minimal (<10%)

Carmustine >250mg/m2

Aldesleukin >12-15 million units/m2

Capecitabine Alemtuzumab

Cisplatin ≥50mg/m2 Amsacrine Cetuxuimab Alpha Interferon

Cyclophosphamide > 1500mg/m2

Arsenic trioxide Cytarabine <100mg/m2 Bevacizumab

Dacarbazine Azacitidine Docetaxal Bleomycin

Procarbazine (po) Busulfan>4mg/d Doxorubicin (liposomal) Bortezomib

Streptozocin Carboplatin Etoposide (iv) Busulfan

Carmustine ≤250mg/m2 Fludarabine (po) Chlorambucil (po)

Cisplatin <50mg/m2 5-Fluorouracil Dasatinib

Cyclophosphamide <1500mg/m2

Gemcitabine Erlotinib

Cyclophosphamide (po) Methotrexate (iv) Fludarabine (iv)

Cytarabine >1g/m2 Mitomycin Gefitinib

Daunorubicin Mitoxantrone Gemtuzumab ozogamicin

Doxorubicin Paclitaxel Hydroxycarbamide

Epirubicin Pemetrexed Lenalidomide

Etoposide (po) Topotecan Melphalan (po)(low dose)

Idarubicin Methotrexate (po)

Ifosfamide Nelarabine

Imatinib Pentostatin

Irinotecan Rituximab

Lomustine Sorafenib

Melphalan >50mg/m2 Sunitinib

Methotrexate 250- >1000mg/m2

Thalidomide

Oxaliplatin Trastuzumab

Temozolomide (po) Vinblastine

Vinorelbine (po) Vincristine

Vinorelbine (iv)

This is only a guide. Each regimen must be considered individually.


13.4 Table 1

Emtogenic Risk Prophylaxis of acute CINV

Prophylaxis of delayed CINV

Options for secondary prophylaxis / breakthrough

emesis

High (>90%) Ondansetron 8mg IV stat Dexamethasone 8mg IV stat (not haem) Aprepitant 125mg po if Cisplatin >70mg/m2, Cyclophosphamide >1500mg/m2

Dexamethsone 2mg tds 3/7 (in regimens not containing a steroid or haematology) Ondansetron 8mg bd 3/7 Aprepitant 80mg days 2 and 3 if given 125mg on day 1. Metoclopramide 10mg tds prn for 5 days

Add in ondansetron 8mg bd 5/7 Consider Levomepromazine 6.25mg prn up to qds Consider Lorazepam 1mg tds, especially in anticipatory nausea. Consider Aprepitant for subsequent cycles (once other options exhausted) if not previously used

Moderate (30-90%)

Ondansetron 8mg IV stat Dexamethasone 8mg IV stat (not haematology)

Dexamethasone 2mg tds 3/7 (in regimens not containing steroids or haem) With Ondansetron 8mg bd 3/7 (anthracycline / cyclophosphamide regimens) Metoclopramide 10mg tds prn for 5 days

Ondansetron 8mg bd 5/7 +/- dexamethasone 2mg tds 3/7 (if not already used) Metoclopramide 10mg tds prn (if not already used) Consider Aprepitant in patients with previously poorly controlled CINV

Low (10-30%) Dexamethasone 8mg IV stat (not haematology)

Metoclopramide 10mg tds prn

Dexamethasone 2mg tds 3/7 (in regimens not containing steroids) With Ondansetron 8mg bd 3/7

Minimal(<10%) None None Metoclopramide 10mg tds prn Dexamethasone 2mg tds 3/7 (in regimens not containing steroids) With Ondansetron 8mg bd 3/7


13.4 References

1. Hesketh PJ: Treatment of chemotherapy-induced emesis in the 1990s: Impact of the 5-HT3 receptor antagonists. Support Care Cancer 2:286-292, 1994

2. De Boer-Dennert M, de Wit R, Schmitz PIM, et al: Patient perceptions

of the side-effects of chemotherapy: The influence of 5HT3 antagonists. Br J Cancer 76:1055-1061, 1997

3. Passik SD, Kirsh KL, Rosenfeld B, et al: The changeable nature of

patients’ fears regarding chemotherapy: Implications for palliative care. J Pain Symptom Manage 21:113-120, 2001

4. Gralla RJ, Osoba D, Kris MG, et al: Recommendations for the use of

antiemetics: Evidence-based, clinical practice guidelines. J Clin Oncol 17:2971-2994, 1999

5. Proposal for classifying the acute emetogenicity of cancer chemotherapy. Hesketh PJ; Kris MG; Grunberg SM; Beck T; Hainsworth JD; Harker G; Aapro MS; Gandara D; Lindley CM, J Clin Oncol 1997 Jan; 15(1): 103-9.

6. Prevention of chemotherapy- and radiotherapy-induced emesis: results of the

2004 Perugia International Ant emetic Consensus Conference. Roila F; Hesketh PJ; Herrstedt J, Ann Oncol. 2006 Jan;17(1):20-8. Epub 2005 Nov 28.

7. American Society of Clinical Oncology guideline for antiemetics in oncology:

update 2006.Kris MG; Hesketh PJ; Somerfield MR; Feyer P; Clark-Snow R; Koeller JM; Morrow GR; Chinnery LW; Chesney MJ; Gralla RJ; Grunberg SM, J Clin Oncol. 2006 Jun 20;24(18):2932-47. Epub 2006 May 22

8. Improved prevention of moderately emetogenic chemotherapy-induced nausea

and vomiting with palonosetron, a pharmacologically novel 5-HT3 receptor antagonist: results of a phase III, single-dose trial versus dolasetron. Eisenberg P; Figueroa-Vadillo J; Zamora R; Charu V; Hajdenberg J; Cartmell A; Macciocchi A; Grunberg S, Cancer 2003 Dec 1;98(11):2473-82.


13.5 Emetic risk category of the radiation administered

Radiation-induced nausea and vomiting (RINV) can be a distressing complication of radiation therapy (RT). The risk of RINV is highest for patients receiving total body irradiation, but it also significant for other types of irradiation as illustrated in the table.

Radiation Emetic Risk Irradiated Area

High (>90 percent) Total body

Moderate (60 to 90 percent)

Half body

Low (30 to 60 percent) Upper abdomen, lower thorax and pelvis; Radio surgery & craniospinal

Minimal (<30 percent) Other sites

The prophylaxis is based on the site of RT and whether it is combined with chemotherapy. When combination treatment is used, prophylaxis is relevant to the most emetic regimen.

The development of new agents to treat chemotherapy-induced emesis and clinical trials in patients with RINV has led to improvements in the control of this radiotherapy complication. The 5-HT3 receptor antagonists and corticosteroids are the most extensively evaluated agents in patients with RINV.

These advances are incorporated into the 2006 American Society of Clinical Oncology guidelines for antiemetics in oncology [1]:

13.51 High and Moderate Risk

For patients receiving total body irradiation (high risk) or half body (moderate risk), prophylactic treatment before each fraction of RT and for 24 hours after the last treatment (Grade 2B)is suggested in this setting, we suggest using a 5-HT3 receptor antagonist as the primary antiemetic (Grade 2B); a corticosteroid may be added depending upon an assessment of the individual patient's risk of developing RINV.

13.52 Low and Minimal Risk

For patients receiving RT with minimal risk of causing emesis, we suggest that routine prophylaxis be deferred, and treatment be administered on an as-needed basis (Grade 2B).

13.6 References 1. American Society of Clinical Oncology guideline for antiemetics in oncology: update 2006.Kris MG; Hesketh PJ; Somerfield MR; Feyer P; Clark-Snow R; Koeller JM; Morrow GR; Chinnery LW; Chesney MJ; Gralla RJ; Grunberg SM, J Clin Oncol. 2006 Jun 20; 24(18):2932-47. Epub 2006 May 22.


14. Management Algorithm for Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) in Oncology

Hyponatraemia <135 mMol/L

Euvolaemic

Serum Osmolality <270 mOsm

Urine Osmolality >100 mOsmol

Elevated Urinary Na+ >25 mEq/l

Exclude

↓T4

↓ Cortisol

Renal failure

Serum Na+ ≥125 mMol/L

or chronic and

asymptomatic

OBSERVE

Hyponatraemia <125 mMol/L

Serum Na+ <110 mMol/L or acute neurological symptoms INTENSIVE CARE

1. Review medications e.g. thiazides. As there may be concomitant dehydration, consider 1L N saline over 4 hours and recheck biochemistry. If sodium has increased continue 1L NS 6 to 8 hourly for 24 hours. 2. Fluid restriction 500mL increasing to 750mL/day.

3. Aim for increase in sodium of no more than 6mmol/L per 24 hours. 4. Consider Demeclocycline 300mg-600mg twice daily. Assess response after one week. If no response, consider Tolvaptan 15mg daily, increasing to 60mg as required. Oncology/Endocrinology Consultant prescribing only.

5. Initial treatment with Tolvaptan may be considered when symptomatic hyponatraemia is preventing urgent anticancer treatments. Oncology Consultant prescribing only.

6. Daily biochemistry while sodium <125mMol/L. 7. Specific anticancer treatment.

Acute Oncology

Medical Review

& Endocrinology

input if required

SIADH

Acute Oncology Clinical

Nurse Specialist

Patient information of

management plan

guidelines for the management of presentations in adults 2014 onc docs/neyhca... · 2015. 4....

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