Handbook of Systemic Treatments for Cancer - 8th Edition

8/10/2019 Handbook of Systemic Treatments for Cancer - 8th Edition

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8th editionGuidelines for the administration of commonly used

anticancer agents and the nursing care of cancer patients

HANDBOOK OF

SYSTEMIC TREATMENTS

FOR CANCER


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ALP alkaline phosphatase

ALT alanine aminotransferase

AML acute myeloid leukaemia

ARDS acute respiratory distresssyndrome

AST aspartate aminotransferase

AV atrioventricular

BB bundle branch

BMD bone marrow depression

BP blood pressure

BCRP breast cancer resistance protein

BUN blood urea nitrogen

CHF congestive heart failure

CNS central nervous system

CPK creatine phosphokinase

CSF cerebrospinal fluid

CVA cerebrovascular accident

CVAD central venous access device

D5W dextrose (glucose) 5%

dpm drops per minute

DRESS drug rash with eosinophilia andsystemic symptoms

DS dextrose 4% + sodium chloride0.18%

DVT deep vein thrombosis

EGFR epidermal growth factor receptor

FBC full blood count

GGT gamma glutamyl transferase

GI gastrointestinal

GORD gastro-oesophageal reflux disease

GvHD graft versus host disease

IA intra-arterialIBD inflammatory bowel disease

ILD interstitial lung disease

IM intramuscular

INR international normalised ratio

IP intra-peritoneal

IV intravenous

LDH lactate dehydrogenase

LFTs liver function tests

LLN lower limit of normal

LVD left ventricular dysfunction

LVEF left ventricular ejection fraction

MAO monoamine oxidase

MI myocardial infarction

NCI CTCAE National Cancer Institute CommonTerminology Criteria for AdverseEvents

NPSA National Patient Safety Agency

NS sodium chloride 0.9%

P-gp P-glycoprotein

PPE palmar plantarerythrodysaesthesia syndrome

PPI proton pump inhibitor

PRES posterior reversibleencephalopathy syndrome

RTI respiratory tract infection

SC subcutaneous

SIADH syndrome of inappropriate

antidiuretic hormone secretionTEN toxic epidermal necrolysis

TIA transient ischaemic attack

TSH thyroid-stimulating hormone

ULN upper limit of normal

UTI urinary tract infection

VEGF vascular endothelial growth factor

VTE venous thromboembolismWBC white blood cell count

WFI water for injection

Abbreviations


3/186Lilly Handbook of Systemic Treatments for Cancer 8th Edition 1

CONTENTS

Acknowledgments 2

Note from the publisher 3

Preface 4

GENERAL GUIDANCE

Systemic anticancer treatment pathway 5

Suggested 24-hr telephone advice for patients having chemotherapy 9

UKONS oncology/haematology helpline triage tool 10

Recommendations for your safety and protection 12

The management of extravasation 15Suggested algorithm for the treatment of extravasation 16

Suggested cytotoxic spillage kit 17

References 18

Further resources 19

Nursing implications of drug side effects 20

DRUG MONOGRAPHS

List of drug monographs 30

Drug monographs 31

References for drug monographs 151

APPENDICES

Appendix 1: Glossary 163Appendix 2: NCI CTCAE v4.0 171

Appendix 3: The cell cycle 174

Appendix 4: Useful formulae 175


4/186February 20142

ACKNOWLEDGMENTS

Lilly Oncology UK and the publisher, Haymarket Medical, would like to acknowledge the following

healthcare professionals for their contributions to updating the administration and nursing guidelines and

drug monographs for the 8th edition of the handbook.

Authors of the 8th edition (2014)

The Royal Marsden NHS Foundation Trust:Lisa Dougherty nurse consultant, IV therapy and lead chemotherapy nurse

Anita McWhirter pharmacy clinical services manager

& the clinical pharmacy team

Greater Midlands Cancer Network:Philippa Jones Macmillan Network lead chemotherapy nurse

Previous editionsWe wish to also extend our special thanks to the following past and present members of staff of the

Royal Marsden Hospital, London and Surrey:

Marilyn Marks and Kerry Jennings for the 1st edition

Val Speechley and Tim Root for the 2nd and 3rd editions

Lisa Dougherty, Julie Mycroft and Tim Root for the 4th edition

Stephen Almond, Judith Earl and Lisa Dougherty for the 6th edition

Lisa Dougherty, Lorraine Hyde, Philippa Jones, Caroline Kay, Louise McNamara, Richard Schorstein and

Anita McWhirter for the 7th edition



Note from the publisher

Welcome to the 8th edition of the Lilly Handbook of Systemic Treatments for Cancer (2014).

The intent of this handbook is to assist healthcare professionals in their day-to-day patient management

by providing concise information and guidelines for the administration of commonly used pharmacological

agents for the treatment of cancer.

The contents of this handbook have been developed collaboratively by nurse and pharmacist teams

at the Royal Marsden NHS Foundation Trust led by Lisa Dougherty and Anita McWhirter, respectively;

in association with the chemotherapy manager and network lead chemotherapy nurse of the Greater

Midlands Cancer Network Philippa Jones, on behalf of Eli Lilly and Company Ltd (Lilly) and the

publisher, Haymarket Medical.

Lillys role, as the sponsor of this handbook, has been limited to checking the factual accuracy of

information on Lilly products and ensuring compliance with the PMCPA Code of Practice for the

Pharmaceutical Industry.

Save for the above, and the compilation of the Appendices section, the updated contents of the handbook

have been developed independently by the authors in collaboration with the publisher.

The monographs in this handbook were compiled from manufacturers summaries of product

characteristics (SPCs) and other established resources. Some of the information presented may reflect

local practice and the clinical expertise of the healthcare professionals involved.

The monographs of the products contained herein are not intended to be a substitute for the

manufacturers SPCs. Only adverse events deemed to be of particular relevance are included.

The publisher has tried to ensure that the information contained in this handbook is accurate and

up-to-date at the time of publication. It is the users responsibility to check for any variation in the

product SPC subsequently. These can be found at www.medicines.org.uk/emc. It is important not to use

copies of the handbook that are out of date or pass on old editions.

The practice guidance presented in this handbook is offered as recommendations, and does not diminish

the requirement for clinical judgment. Readers are strongly advised to check these recommendations

against their local protocols and guidelines and to make their own further enquiries of manufacturers

or specialists in relation to particular drugs, treatments or advice. Lilly, the publisher and the authors

cannot accept liability for errors or omissions, and disclaim any liability arising out of the use of this

handbook in practice.

2014 Lilly Oncology UK.

No part of this publication may be reproduced. Not for resale.

Published by Haymarket Medical, Teddington Studios, Broom Road, Teddington TW11 9BE.

Printed by Cardiff Printing Company, Llantrisant, South Wales.

Date of preparation: February 2014; UKONC00326

Haymarket is certified by BSI toenvironmental standard ISO14001


6/186February 20144

Preface

The range of systemic anticancer therapies has increased dramatically and within the past year over 20

new therapies have become widely available. For the last edition, a change in the title of the handbook

from Cancer Chemotherapy to the Handbook of Systemic Treatments for Cancer, reflected the inclusion

of newer agents that are not purely cytotoxic in nature, such as those targeting specific molecular

receptors and cell signalling pathways.

This handbook is a Lilly initiative to help improve patient care and continues to be used as a definitive

reference and guide to practice by nurses, doctors and pharmacists. The 8th edition updates the existing

84 monographs and includes 24 new drugs. Evidence to support the text has been provided, underpinned

by the principles in the Cancer Services Manual, the requirement of peer review standards and a

comprehensive reference list.

Contributions to this updated edition have been from nursing staff that are involved in the assessment

of patients and the adminstration of chemotherapy on a daily basis, and pharmacists who are involved in

the dispensing and preparation of systemic anticancer therapy, as well as in giving advice to both staff

and patients. It is hoped that all healthcare professionals will find this updated guide useful, and that it

continues to meet their needs in the clinical setting.

Editor

Lisa Dougherty

Nurse consultant, IV therapy and lead chemotherapy nurse, The Royal Marsden NHS Foundation Trust

Ordering additional copies of the handbook

If you would like to order additional copies of the

HANDBOOK OF SYSTEMIC TREATMENTS FOR CANCER

or register your interest to receive future editions, please visit

www.lillyoncology.co.uk



Systemic anticancer treatment pathway

A number of national reports and guidelines recommend the implementation of key steps in the systemicanticancer treatment (SACT) pathway to ensure the safe and appropriate delivery of treatment.

The pathway presented here has been developed to reflect the recommendations contained in the followingdocuments:

1. For better, for worse? National Confidential Enquiry into Patient Outcome and Death, November 2008.12. Chemotherapy Services in England: Ensuring quality and safety. A report from the National

Chemotherapy Advisory Group, 2009.2

3. Manual for Cancer Services: Chemotherapy Measures (2.0), 2013.3

Prior to commencing a course of treatmentIt is recommended that the key actions shown below are taken prior to commencing a course of treatmentand it is advisable that there is a procedure in place to check that this happens.

2 Physical assessment1,3

The results of a comprehensive assessment of the patients physical condition and suitability fortreatment should be recorded. This will include a record of the patients performance status at thetime of the decision to treat.

Baseline observations of BP, pulse and respiratory rates should be taken and recorded as pertreatment protocol.

Baseline blood tests should be performed including FBC, urea and electrolytes and renal function. Treatment- or disease-specific investigations, for example specific tumour markers, should

be performed. The results of all pre-treatment investigations should be reviewed prior to treatment

administration.

1 Decision to treat, consent and treatment plan1-3

The decision to initiate the course of SACT should have been made at consultant level unless thereare exceptional circumstances.

There should be a completed standardised consent form that includes reason for and intention oftreatment, as well as common and serious toxicities which have been discussed with the patient.

Patients should be fully involved in decision-making regarding their care and treatment.Written information should always be provided for the patient and this should be recorded on theconsent form.

There should be a treatment plan for each course of SACT detailing: Diagnosis and staging according to an internationally recognised staging system

Performance status and co-morbidities Treatment intent Tests required pre-SACT Planned number of cycles Frequency and method of assessment of response to treatment Any deviation from protocol and reason for this

This treatment plan should be authorised and signed by a consultant oncologist orhaemato-oncologist.


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4 Prescribing and dispensing3

Prescribing, prescription verification and dispensing of SACT should only be undertaken byappropriately trained staff.

All SACT prescriptions should be checked by an oncology pharmacist who has undergone specialisttraining, demonstrated appropriate competence and is locally authorised/accredited for the task.

3 The individual assessment by oncology nurses/pharmacists prior to the start of the course of SACTshould include1

Patient and carer information, education, support and advice. Each patient should be provided with a card containing key information about the treatment and

contact details of the 24-hr telephone advice service that is available for patients receiving SACT. The importance of contacting the telephone advice service, if there are worries about symptoms

that may be related to treatment, should be explained clearly.

6 Discharge following administrationThe following checks should be performed prior to allowing the patient to go home: The patient should have all the supportive drugs they are prescribed and understand the

importance of taking them as instructed. The patient should have an appointment for their next cycle and/or review. The patient should have a request form for pre-treatment investgations if required. Reinforce the availability of the 24-hr telephone advice service.

5 Administration of treatment3,4

Administration should only be undertaken by appropriately trained nurses who have been deemedcompetent by their employing organisation.

All SACT should be checked by a second nurse prior to administration. The prescription should be checked against the patient with the following details confirmed:

patient identity, allergy status, consent, patient understanding of the SACT they are to receive andtheir fitness to receive treatment.

The prepared drugs should be checked to ensure they match the prescription for date, dose andpatient details, as well as checking the volume, route of administration, diluent, correct method(infusion or bolus injection) and expiry date/time.

The patient should have an appropriate vascular access device (VAD) in situ or one should beinserted by an appropriately trained nurse.

During administration, the nurse should monitor the patient and the VAD site for any side effectsand manage them accordingly.

The nurse should wear appropriate personal protective clothing and dispose of all equipment inthe appropriate sharps bins or clinical waste bags.



Prior to commencing each cycle of treatmentTo ensure continued safe and appropriate delivery of SACT, it is vital that the following key actions are takenprior to commencing each cycleof treament and it is advisable that there is a procedure in place to checkthat this happens.

2 Pre-treatment review

Treatment plan are there any changes to the plan, for example dose modifications or alterationsto supportive medications? Have these changes happened?

Assessment of response should the patient have had a senior review and necessaryinvestigations to assess response to treatment prior to this cycle? Has this been completed?

1 Pre-treatment assessment1-3

The results of an assessment of the patients physical condition and suitability for treatment should berecorded, including:

Assessment of toxicityClinicians assessing patients for SACT must perform a full assessment of toxicities that the patient mayhave experienced at any time since receiving their previous cycle of treatment. This assessment shouldbe recorded in the patients treatment record and any significant toxicity experienced by the patientshould be discussed with the prescriber prior to treatment administration as there may be a need tomodify the treatment plan. The Manual for Cancer Services: Chemotherapy Measures, recommends the

use of the National Cancer Institutes Common Terminology Criteria for Adverse Events (CTCAE).3,5

Physical assessment A review and record of the patients performance status with action taken if deterioration is noted.

The Manual for Cancer Services: Chemotherapy Measures recommends the use of the WHOsystem for grading of performance status, but the Eastern Co-operative Oncology Group (ECOG)system can also be used.3,6

Observations and recording of BP, pulse and respiratory rates, temperature and body weight,as indicated

Standard blood tests, including FBC, urea and electrolytes and renal function, should beperformed. The results should be within acceptable/agreed treatment parameters.

Treatment- or disease-specific investigations, such as specific tumour markers, mustbe performed.

The results of all pre-treatment investigations should be reviewed prior to treatment administration.

3 Patient and carer information, education, support and advice3

The provision of information, education and support is an ongoing process and the needs andrequirements of the patient should be assessed regularly throughout treatment. The assessmentand any action arising from it should be recorded in the patients medical record.

The importance of contacting the 24-hr telephone advice service, if the patient is worried about

symptoms that may be related to their treatment, should be reinforced throughout treatment.


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4 Prescribing and dispensing3

Prescribing, prescription verification and dispensing of SACT should only be undertaken byappropriately trained staff.

All SACT prescriptions should be checked by an oncology pharmacist, who has undergonespecialist training, demonstrated their appropriate competence and is locally authorised/accredited for the task.

6 Discharge following administrationThe following checks should be performed prior to allowing the patient to go home: The patient should have all the supportive drugs they are prescribed and understand the

importance of taking them as instructed. The patient should have an appointment for their next cycle and/or review. The patient should have a request form for pre-treatment investigations if required.

5 Administration of treatment3,4

Administration should only be undertaken by appropriately trained nurses who have been deemedcompetent by their employing organisation.

All SACT should be checked by a second nurse prior to administration. The prescription should be checked against the patient to confirm patient identity, allergy status,

consent and fitness to receive treatment. The prepared drugs must be checked to ensure they match the prescription for date, dose and

patient details as well as volume, route, diluent, correct method (infusion or bolus injection) andexpiry date/time. The patient should have an appropriate vascular access device (VAD) in situ or one should be

inserted by an appropriately trained nurse. During administration, the nurse should monitor the patient and the VAD site for any side effects

and manage them accordingly. The nurse should wear appropriate personal protective clothing and dispose of all equipment in

the appropriate sharps bins or clinical waste bags.

7 End of treatment3

Following the final cycle of a course of treatment, the patient and their primary care team should beprovided with a plan for further care and informed who will take responsibility for its provision.



Suggested 24-hr telephone advice for patients having chemotherapy

The Manual for Cancer Services: Chemotherapy Measures recommends that cancer networks andacute trusts ensure that patients receiving SACT who may be experiencing side effects or complicationsrelated to their treatment have access to 24-hr telephone advice on how to obtain help and treatment. 3The United Kingdom Oncology Nursing Society (UKONS) central west chemotherapy nurses group hasdeveloped a 24-hr triage tool that can be used to risk-assess patients who contact a helpline or present as

an emergency.7UKONS recommend that there be a programme of training and assessment of competencyprior to using the tool; however, a brief explanation of the assessment process and a copy of theassessment tool are included in this book for your information.

The UKONS 24-hr triage tool is a recognised tool that is a simple, reliable, evidence-based process thatgrades toxicities according to the significance of presenting symptoms and advises action accordingly.

It identifies patients who require: Referral to acute oncology teams for urgent assessment Clinical monitoring or review

The risk assessment process includes a Red Amber Green (RAG) cumulative scoring system to guidedecision-making. It is important that the effects of treatment are not underestimated and that thesignificance of the cumulative effects of a number of lower-level toxicities is recognised.

Risk assessment processIt is vitally important that the process is methodical and thorough in order for it to be useful and providean accurate triage assessment.

There are a number of questions to ask and information that will need to be collected to make sure thatthe correct advice is given.

Step 1The user moves methodically down the triage assessment tool, asking appropriate questions, forexample, does the patient have any nausea?If NO, tick greenand move on.If YES, use the questions provided to help you grade the problem and tick either amberor red.

Step 2Advice is given and action taken according to the guidelines below:

RED any toxicity graded here takes priority and assessment should follow immediately. Redtriage requires face-to-face consultation and assessment by an appropriately trained and qualifiedmember of the clinical team. This assessment should take place in a suitable area that has accessto investigation and treatment facilities. Patients should be asked to attend as soon as possible forassessment.

x2 AMBER two or more amber toxicities should be escalated to red. Action and assessment shouldfollow immediately.

AMBER a single amber toxicity should be reviewed/followed up within 24 hrs. This may be atelephone consultation or an urgent review clinic appointment. The caller should be instructed to callback if they continue to have concerns or their condition deteriorates.

GREEN patients should be given reassurance that the problem at present does not give cause for

concern but they should be vigilant and if the situation gets worse or does not improve they should callback immediately.

Step 3

A record of the assessment and advice given should be made in the patients medical record.


12/18610 February 201410

GRADE GRADE GRADE GRADE

TOXICITY 0 1 2 3 4

Feverand receiving cytotoxic chemotherapyor immunocompromised

IF TEMP 37.5C or ABOVE or BELOW 36C or GENERALLY UNWELL URGENT Assessment AND MEDICAL REVIEW Follow neutropenia pathwayALERT Pts on steroids/analgesics or dehydrated may not present with pyrexia but may still have infection (If in doubt do a count)

Chest painOnset? What makes it worse?Radiation? Any cardiac historySTOP CAPECITABINE or INFUSIONAL SFU

None Advise URGENT A&E for medical assessment

Performance StatusHas there been a recent change in performance status?

Asymptomatic Symptomatic but completelyambulant

Symptomatic, 50% in bed, butnot bed bound

Bed bound

NauseaHow many days? What is the patients oral intake?Is the patient taking antiemetics as prescribed?Access patients urinary output

None Able to eat/drink reasonableintakeReview antiemetics asprescibed

Can eat/drink but intakesignificantly decreasedReview antiemetics according tolocal policy

No significant intakeArrange urgent assessmentand review

VomitingHow many days/episodes?What is the patients oral intake?Does the patient have constipation or diarrhoea?(see specific toxicity)Assess patients urinary output

None 1 episode in 24 hoursReview antiemetics asprescibed

2-5 episodeds in 24 hoursReview antiemetics according tolocal policy

6-10 episodes in 24 hoursArrange urgent assessmentand review

>10 episodes in 24 hoursArrange urgent assessmentand review

Oral/stomatitisHow many days?Is there evidence of mouth ulcers?Is there evidence of infection?Are they able to eat/drink?Assess patients urinary output

None Painless ulcers, erythema, mildsoreness able to eat/drinkUse mouthwash asrecommended

Painful erythema. oedema orulcers but can eat/drinkContinue to use mouthwash,drink plenty of fluids. Usepainkillers either as a tablet ormouthwash

Painful erythema difficultywith eating and drinkingArrange urgent assessmentand review

Mucosal necrosis and/orrequires parenteral or enteralsupportArrange urgent assessmentand review

DiarrhoeaConsider infection!How many days has this occurred for?How many times in a 24hr period?Does the patient have any abdominal pain/discomfort?

For how long? Has the patient taken any medication?See specific toxicity for painNB. If taking CAPECITABINE chemotherapy, follow

specific pathway

None Increase to 2-3 bowelmovements a day overpre-treatment movementsDrink more fluidsObtain stool sample

?consider regimen specificantidiarrhoeal

Increase to 4-6 episodes a day ornocturnal movement/ moderatecrampingDrink plenty of fluidsObtain stool sample

?obtain regimen specificantidiarrhoeal

Increase to 7-9 episodes a dayor incontinenceSevere crampingArrange urgent assessmentand review

Increase to >10 episodes a dayor grossly bloody diarrhoea orneed for parenteral supportArrange urgent assessmentand review

ConstipationHow long since bowels opened?What is normal?Doed the patient have any abdominal pain/vomiting?Has the patient taken any medication?

None Mild no bowel movement inlast 24 hoursDietary advice, increase fluidintake, review supportivemedication

Moderate no bowel movementin last 48 hoursIf associated with pain/vomitingmove to redReview fluid and dietary intakeRecommend laxative

Severe no bowelmovement in last 72 hoursArrange urgent assessmentand review

Paralytic ileum >96 hoursArrange urgent assessmentand review

FeverNOT receiving chemotherapy Normal n/a >37.5C - 38CCheck in 1 hr and contact againif still pyrexial see red

>38-40CArrange urgent assessmentand review

>40CArrange urgent assessmentand review

Infection If Pyrexial see fever toxicityHas the patient taken their temperature? When?Has the patient experienced any shivering, chills or shakingepisodes?

None Generally well Generally wellArrange Review

Severe symptomaticinfectionArrange urgent assessmentand review

Life threatening sepsisArrange urgent assessmentand review

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TRIAGE TOOLONCOLOGY/HAEMATOLOGY HELPLINE

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Palmar - plantar syndromeNB. If taking CAPECITABINE chemotherapy, follow

specific pathway

N one Numbness, tingling, painlesserythema and swellingAdvise patient to rest handsand feet. Use emolient cream

Painful erythema and swelling? Arrange review(mayrequire dose reduction or defertreatment). Advise analgesia

Moist desquamation,ulceration, blistering andsevere painArrange review (may require

dose reduction or defertreatment)Advise analgesia

FatigueHow many days has this occured for?Any other associated symptoms?

None Increased fatigue but notaltering normal activitiesRest accompanied withintermittent mild activity

Moderate or causing difficultyperforming some activities? Arrange review

Severe or loss of ability toperform some activitiesArrange review

Bedridden or disablingArrange urgent assessmentand review

AnorexiaWhat was their weight before? What is appetite like?Any contributory factors e.g. dehydration, diarrhoea,vomiting, mucositus and nausea? link to specific toxicity

None Loss of appetite withoutalteration in eating habitsDietary advise

Oral intake altered withoutsignificant weight loss ormalnutrition:? Arrange review

Oral intake altered inassociation with significantweight loss/malnutritionArrange urgent assessmentand review

Life threatening complicationse.g. collapseArrange urgent assessmentand review

Dyspnoea/shortness of breathIs it a new symptom? Is dyspnoea worsening?Is there any chest pain? link to specific toxicityHow long for?What can the patient do? (? alteration in PS)CONSIDER SVCO/ANAEMIA/PULMONARY EMBOLISM

None No new symptoms Dyspnoea on exertion? Arrange review

Dyspnoea at normal levelof activityWill need urgent assessmentand review

Dyspnoea at rest or requiringventilatory supportArrange urgent assessmentand review

RashIs it localised or generalised?How long has it been there?

Any signs of infection? Is it itchy?HAEMATOLGY FOLLOW LOCAL GUIDANCE

None Macular or papular eruptionor erythema withoutassociated symptoms

Localised rash, otherwise well

Macular or papular eruption orerythema with Pruritus or otherassociated symptoms

Arrange review

Symptomatic unwellArrange urgent assessmentand review

Symptomatic unwellArrange urgent assessmentand review

Neurosensory/motorWhen did the problem start? Is it continuous?Is it getting worse? Is it affecting mobility/functionAny constipation or urinary incontinence?Consider Spinal Cord Compression

None Mild parasthesia, subjectiveweakness; no objectivefindingsMonitor and contactimmediately if deteriorates

Mild or moderate sensory loss,moderate parasthesia, mildweakness with no loss of functionImmediate contact if deterioratesArrange review

Severe sensory loss,parasthesia or weakness thatinterferes with functionArrange urgent assessmentand review

ParalysisArrange urgent assessmentand review

BleedingIs it a new problem? Is it continuous? What amount?Where from? Is the patient on anticoagulants?HAEMATOLOGY FOLLOW LOCAL POLICY

None Mild self limited controlled byconservative measures

Gross 1-2 unitsUrgent assessment to A&E

Gross 3-4 units per episodeUrgent assessment to A&E

Massive >4 units per episodeUrgent assessment to A&E

PainIs it a new? Where is it? How long have you had it?Have you taken any analgesia?Consider thrombosis? Any swelling/redness?

None Mild painNot interfering with functionAdvise/discuss analgesea

Has painPain or analgesea interferingwith function, but not ADLArrange review

Severe painPain or Analgesia interferingADLArrange urgent assessmentand review

Severe pain, disabling!Arrange urgent assessmentand review

BruisingIs it a new problem? Is it local/generalised?Is there any trauma involved?

None Petechia/bruising, localisedArrange review

Moderate Petechia/purpuraGeneralised bruisingArrange urgent assessmentand review

Generalised petechia/purpuraArrange urgent assessmentand review

ExtravasationAny problems immediately after administration?When did the problem start?Is the problem around the injection site?Has the patient got a central venous catheter?Explain the reaction?

Non vesicantReview next day

VesicantArrange urgent assessmentand review

4 P. Jones et al/UKONS/GMCN Endorsed by:


13/186February 201412

Recommendations for your safety and protection

The following recommendations concern the safe reconstitution and handling of cytotoxic agents inorder to prevent self contamination. Ideally, all drugs will be reconstituted by trained pharmacy staff in amicrobiological safety cabinet or isolator. Where a nurse may be required to reconstitute a cytotoxic drugit must be carried out in an isolator that is not on the ward/department or by using a closed reconstitutiondevice. It should only be carried out when absolutely necessary. Local instructions for isolator use should

be followed.8,9

The administration of SACT

1 General1.1 All drugs should be handled with respect, taking great care to avoid spillage.8

1.2 A pre-treatment assessment should be carried out folowing the steps in the pre-treatment pathway(pages 5-8). Drug dosage (according to the protocol) should be checked prior to administration ofany SACT.1,3,8,10

1.3 Strict aseptic technique should be observed at each stage of the procedure, for example, when

adding any drug to an IV solution or via an administration set/injection cap.10

2 RoutesThere are a number of routes for the administration of SACT.

2.1 Oral

The term oral anticancer medicine refers to drugs with direct antitumour activity, administered viathe oral route, including traditional cytotoxic chemotherapy (eg, capecitabine, vinorelbine), small-molecule treatments (eg, imatinib, erlotinib) and other agents such as thalidomide.8

2.2 Intravenous

This is the administration of cytotoxic drugs via a peripheral or central vein. It is the most commonlyused route of administration.8

2.2.1 Vein selectionThe vein used should be firm, bouncy, straight and, if possible, previously unused. Bruisedand inflamed areas should be avoided. Ideally the injection or infusion should be giveninto a large, easily visible, superficial vein. Any limb with a compromised circulation, forexample, as a result of mastectomy, lymphoedema, thrombophlebitis or trauma, should beavoided.11The antecubital fossa should be avoided, especially when administering vesicantdrugs.8,11In everyones interest, it is suggested that a practitioner should have no more than

two attempts at device placement and should then seek the advice of a more experiencedpractitioner.11Where no suitable veins are available or the patient is to receive regularadministration of highly irritant/vesicant infusions, then consideration should be given to theplacement of a CVAD.8

2.2.2 Device selectionCannulae (22 or 24g) should be selected following vein assessment, choosing the smallestgauge and shortest length appropriate for the type and length of therapy. The smaller thedevice, the less trauma to the vein and the better the blood flow around the device. Thisincreases dilution and rapid removal of the irritant and makes chemical phlebitis less likely.However, longer cannulae (22 or 20g) may be necessary to reduce the risk of dislodgment or

associated infiltration and extravasation.8



2.2.3 Administration

(a) Each device must always be tested with NS before injecting SACT, and similarly flushedafter administration. If several drugs are to be given, the device should be flushed aftereach one to prevent possible interactions. This can be accomplished by attaching anddetaching a syringe of NS after each drug or by attaching a compatible infusion to thedevice and using one of the following techniques:10

(i) A fast-running infusion into which the drug is administered simultaneously via

the side arm if the vein can accommodate it or if this method is specified in theliterature. This is useful for highly irritant drugs but may not be necessary whenadministering via a CVAD.

(ii) A stop/start flushing technique if the vein is fragile or small and cannotaccommodate a large fluid flow.

(b) Any drug known to be a vesicant should be given first when multiple drugs areprescribed (but after any pre-medication). It is at this time that the integrity of the veinis greatest and extravasation is least likely. For practical reasons, drugs to be given byinfusion, for example, dacarbazine, should be administered last.8,11

(c) A number of cytotoxic drugs are vesicant and will cause extreme tissue damage if

leakage occurs from the vein. Even a very small leak is a serious situation and caremust be taken to ensure that all the drug enters the vein. Consequently, drugs shouldbe given slowly and the area around the device observed throughout the administration.8The practitioner should regularly assess the comfort of the patient, observe the site forswelling or skin colour changes and check vein patency by checking for blood return.8Ifthe nurse has any doubt about the patency of the device and vein then the administrationshould stop and the site should be checked before continuing. If extravasation issuspected then follow the management of extravasation guidance on page 15. 8,11

(d) Drug solutions that are stored in the refrigerator may cause venospasm and an achingsensation along the vein. It is important to distinguish between this and the sharpburning sensation which may indicate the extravasation of a vesicant.8

(e) With repeated injections of some drugs, veins may become very sensitive. The key iseither to dilute the drug or increase vasodilation. The following may help:(i) Inject the drug slowly or administer as an infusion.(ii) Make use of frequent NS flushes.(iii) Give the injection via a fast-running NS infusion.(iv) Use the smallest gauge cannula to increase blood flow around the device and

ensure more rapid circulation of the drug.(v) Apply a heat pack above the cannula site to increase vasodilation.

2.3 Intrathecal

This is the administration of cytotoxic drugs into the CNS via the CSF using a lumbar puncture.8

SACT administered via this route has the potential to cause great harm and has been associatedwith the deaths of at least 13 patients since 1985. Since 2001, all Trusts that administer intrathecalSACT have been required to comply with the national guidance on safe administration, mostrecently updated in 2008.12,13 Guidance issued by the NPSA means that from 2013, Trusts mustnow ensure that all spinal (intrathecal) bolus doses and lumbar punctures are performed usingsyringes, needles and other devices with connectors that cannot connect with intravenous Luerconnectors.14,15


15/186February 201414

The key requirements of the 2008 guidance include:12

Only trained, designated personnel whose names are recorded on the appropriate intrathecalregister are authorised to prescribe, dispense, check or administer intrathecal SACT.

All staff involved in the intrathecal SACT process must undertake a formal competency-basedinduction programme and update annually.

In adults, IV drugs must be administered BEFORE intrathecal drugs are issued (or afterIV continuous infusions have been started).

Children receiving intrathecal therapy under general anaesthetic will have their intrathecaltreatment first in theatre. IV drugs (excluding vinca alkaloids) may be given later in day care or onthe ward, but never in theatre.

Intrathecal chemotherapy should always be administered in a designated area, within normalworking hours; out-of-hours administration must only occur in exceptional circumstances.

Checks must be made by medical, nursing and pharmacy staff at relevant stages throughout theprescribing, preparation and administration process.

This guidance predominantly relates to treatment given intrathecally, by lumbar puncture

(via spinal injection) but is also relevant to intra-ventricular chemotherapy (via injection into theventricles of the brain).



The management of extravasation

Extravasation is the leakage of vesicants (any solution or medication that causes the formation of blisterswith subsequent tissue necrosis and may be DNA- and non-DNA binding) into local tissue. It requiresimmediate action if local tissue damage is to be prevented. If any doubt arises about patency of the vein,the injection or infusion should be stopped and recommenced in another vein if necessary, preferably inthe other arm. If this is not possible, use of a vein proximal to that already used will prevent leakage from

the earlier puncture site.8,16

Extravasation should be suspected if:8

the patient complains of a sharp stinging or burning sensation around the cannula site. swelling or leakage occurs at the site of the cannula. no flashback of blood is obtained (but absence of this, seen alone, is not necessarily an indication

of extravasation). resistance is felt on the plunger of the syringe during bolus administration. free flow of fluid is absent if an infusion is in progress.

When using a CVAD, blood return must always be established prior to administration.17If there is no bloodreturn, the Trust should have a local policy that describes the steps to be taken by the practitioner in orderto ascertain that the tip of the CVAD is in the correct position. Prevention is key and nurses should knowwhich patients are at most risk.

Clinical practice guidelines on the management of extravasation have been issued by the European Societyfor Medical Oncology (ESMO) and the European Oncology Nursing Society (EONS); however, guidance mayvary according to local policy.18,19 The policy detailed here is the current policy of the Royal Marsden NHSFoundation Trust. It is included for reference only. All staff who administer SACT should ensure that theirTrust or hospital develops its own extravasation policy.


17/186February 201416

SUGGESTED ALGORITHM FOR THE TREATMENT OF EXTRAVASATION

SUSPECT EXTRAVASATION IF:(a) Patient complains of burning or stinging pain OR(b) There is evidence of swelling, induration, leakage at site OR(c) There is resistance on plunger of syringe or absence of free flow of infusion OR(d) There is no blood return (if found in isolation via a peripheral cannula this should not be regarded as an indication

of a non patent vein. However, in the event of no blood return from a CVAD follow algorithm for persistentwithdrawal occlusion)

ELEVATE THE LIMB

Apply hydrocortisone cream to reduce local inflammation. Where appropriate apply dimethyl sulfoxide every 2 hrs for24 hrs and then 6 hourly for up to 7 days

Document in duplicate one copy in patients notes and one copy to the nurse consultant IV therapy. Complete a clinicalincident form

INFORM THE MEDICAL STAFF

GIVE PATIENT A PATIENT INFORMATION SHEET

CATEGORY A DRUGSVinca alkaloids, paclitaxel Inject 1500 iu hyaluronidase

SC around the site Apply a warm pack to aid

absorption of hyaluronidase Warm pack to remain in situ

for 2-4 hrs

STOP THE INJECTION / INFUSION WITHDRAW AS MUCH OF THE DRUG AS POSSIBLE (INJECTION ONLY) REMOVE THE PERIPHERAL CANNULA COLLECT THE EXTRAVASATION PACK CONSIDER CONTACTING THE EXTRAVASATION TEAM TO PERFORM FLUSH OUT TECHNIQUE

CATEGORY B DRUGSDactinomycin, dacarbazine, daunorubicin, doxorubicin,epirubicin, idarubicin, mitomycin C, streptozocin, trabectedin

Apply cold pack to cause vasoconstriction for

15-20 mins, 3-4 times a day for at least 24 hrsIf extravasation is with any of the following: mitomycin C,doxorubicin, idarubicin, epirubicin, dactinomycin

Draw around area of extravasation with indelible pen

Put on gloves

Apply thin layer of dimethyl sulfoxide topically to the

marked area using the small plastic spatula in lid ofthe bottle

Allow it to dry and apply gauze This should be applied within 10-25 minsIf extravasation of doxorubicin, idarubicin, epirubicin ordaunorubicin occurs (ie, 3.5ml or more peripherally orany volume via a CVAD), then stop cold pack, do not applydimethyl sulfoxide and contact member of extravasationteam to advise on use of dexrazoxane



Suggested cytotoxic spillage kit8

Particulate respirator mask

Plastic apron Gown Paper towels Plastic bucket Copy of spillage procedure

Essential equipment

Two plastic overshoes

Two disposable armlets Two clinical waste bags Two pairs of disposable non-sterile latex or

nitrile gloves Goggles (non-disposable): EN 166-8

1 Act immediately. Assess the level of exposure of any individual and isolate them from the spill.

2 Collect spillage kit.

3 Put on both pairs of gloves, goggles and a gown and then a disposable plastic apron over the gown.Ifthere is visible powder spill, put on a good-quality particulate respirator mask.Ifspillage is on the floor, put on overshoes.

Procedure

4 Wipe up powder spillage quickly with well dampened paper towels, starting at the outer edge of the spillarea and working in a circular motion towards the middle to contain spill and dispose of them as high-risk waste.

5 Mop up liquids which have been spilled on a hard surface with paper towels, starting at the outer edge ofthe spill area and working in a circular motion towards the middle to contain spill and dispose of them ashigh-risk waste.

6 Wash hard surfaces at least twice with copious amounts of cold, soapy water and dry with paper towels.The floor should then be given a routine clean as soon afterwards as possible. If spillage has occurred ona carpet it will require cleaning as soon as possible.

Ifspillage is on clothing, remove it as soon as possible and treat as soiled linen.Ifspillage has penetrated clothing, wash contaminated skin liberally with soap and cold water.Ifspillage is on bed linen put on gloves and an apron, change it immediately and treat as soiled linen.Ifan accident or spillage involving direct skin contact occurs, the area should be washed thoroughly with

soapy water as soon as possible. In the event of a cytotoxic splash to the eye, irrigate thoroughly with NS ortap water for at least 15 minutes.

Post-procedure

7 Any accident or spillage by nursing staff involving direct skin contact with a cytotoxic drug must bereported to the occupational health department and manager as soon as possible after the first aid isperformed and appropriate documentation completed.


19/186February 201418

References

1. National Confidential Enquiry into Patient Outcome and Death. For better, for worse? A review of the care of patientswho died within 30 days of receiving systemic anti-cancer therapy. London, NCEPOD, 2008. Available from: http://www.ncepod.org.uk/2008report3/Downloads/SACT_report.pdf (accessed 14 January 2014).

2. National Chemotherapy Advisory Group. Chemotherapy services in England: Ensuring quality and safety. London,NCAG, 2009. Available from: http://webarchive.nationalarchives.gov.uk/20130107105354/http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/documents/digitalasset/dh_104501.pdf (accessed 14 January 2014).

3. National Cancer Peer Review - National Cancer Action Team. National Cancer Peer Review Programme. Manualfor Cancer Services: Chemotherapy Measures, v2.0. London, NCAT, 2013. Available from: http://www.cquins.nhs.uk/?menu=resources (accessed 14 January 2014).

4. Nursing and Midwifery Council. Standards for medicines management. London, NMC, 2010. Available from:http://www.nmc-uk.org/Documents/NMC-Publications/NMC-Standards-for-medicines-management.pdf (accessed14 January 2014).

5. US Department of Health and Human Services, National Institutes of Health, National Cancer Institute. CommonTerminology Criteria for Adverse Events (CTCAE) v4.03; June 2010. NIH Publication No.09-5410. Available from: http://www.eortc.be/services/doc/ctc/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf (accessed accessed 14 January 2014).

6. Oken MM, Creech RH, Tormey DC et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group.Am JClin Oncol 1982; 5: 649-55.

7. UK Oncology Nursing Society. Oncology/Haematology 24-hour triage rapid assessment and access tool. October 2010.

Available from: http://www.ukons.org/ (accessed 14 January 2014).8. Hall K, Hyde L, Schorstein R. Chapter 19. Cytotoxic therapy. In: Dougherty L, Lister S (eds). The Royal Marsden Hospital

Manual of Clinical Nursing Procedures. 8th edition. Oxford, Wiley-Blackwell, 2011.9. Health and Safety Executive. Safe handling of cytotoxic drugs. HSE Information Sheet MISC615. London, HSE, 2003.

Available from: http://www.hse.gov.uk/pubns/misc615.pdf (accessed 14 January 2014).10. Dougherty L. Chapter 10. Intravenous management. In: Brighton D, Woods M (eds). The Royal Marsden Hospital

Handbook of Cancer Chemotherapy a guide for the multidisciplinary team . Edinburgh, Elsevier ChurchillLivingstone, 2005.

11. Dougherty L. Chapter 9. Obtaining peripheral venous access. In: Dougherty L, Lamb J (eds). Intravenous Therapy inNursing Practice. 2nd edition. Oxford, Blackwell, 2008.

12. Department of Health. Health Service Circular. HSC 2008/001 Updated national guidance on the safe administrationof intrathecal chemotherapy. London, DH, 2008. Available from: http://webarchive.nationalarchives.gov.

uk/20130107105354/http://www.dh.gov.uk/prod_consum_dh/groups/dh_digitalassets/documents/digitalasset/dh_086844.pdf (accessed 14 January 2014).

13. National Patient Safety Agency. Using Vinca Alkaloid Minibags (Adult/Adolescent Units) NPSA/2008/RRR004. London,NPSA, 2008. Available from: http://www.nrls.npsa.nhs.uk/alerts/?entryid45=59890 (accessed 14 January 2014).

14. National Patient Safety Agency. Safer spinal (intrathecal), epidural and regional devices - Part A: update. NPSA/2011/PSA001. London, NPSA, 2011. Available from: http://www.nrls.npsa.nhs.uk/alerts/?entryid45=94529 (accessed 14January 2014).

15. National Patient Safety Agency. Safer spinal (intrathecal), epidural and regional devices Part B. NPSA/2009/PSA004B.London, NPSA, 2009. Available from: http://www.nrls.npsa.nhs.uk/alerts/?entryid45=94529 (accessed 14 January 2014).

16. Dougherty L. IV therapy: recognizing the differences between infiltration and extravasation. Br J Nurs2008; 17: 896,898-901.

17. Masoorli S. Extravasation injuries associated with the use of central vascular access devices.JVAD2003; 8: 21-3.

18. Prez Fidalgo JA, Garca Fabregat L, Cervantes A et al; ESMO Guidelines Working Group. Management of chemotherapyextravasation: ESMO-EONS Clinical Practice Guidelines.Ann Oncol2012; 23 Suppl 7: vii167-73.

19. Dougherty L, Oakley C. Advanced practice in the management of extravasation. Cancer Nursing Practice2011; 10: 16-22.20. Polovich M, Whitford JM, Olsen M. Chapter VII. Side Effects of Cancer Therapy. In: Polovich M, Whitford JM, Olsen M

(eds). Chemotherapy and Biotherapy Guidelines and Recommendations for Practice. 3rd edition. Pittsburgh, OncologyNursing Society, 2009.

21. Dolan S. Chapter 21. Anaemia. In: Brighton D, Woods M (eds). The Royal Marsden Hospital Handbook of CancerChemotherapy a guide for the multidisciplinary team. Edinburgh, Elsevier Churchill Livingstone, 2005.

22. Dougherty L. Chapter 23. Alopecia. In: Brighton D, Woods M (eds). The Royal Marsden Hospital Handbook of CancerChemotherapy a guide for the multidisciplinary team. Edinburgh, Elsevier Churchill Livingstone, 2005.

23. Dolan S. Chapter 25. Electrolyte abnormalities. In: Brighton D, Woods M (eds). The Royal Marsden Hospital Handbookof Cancer Chemotherapy a guide for the multidisciplinary team. Edinburgh, Elsevier Churchill Livingstone, 2005.

24. Wolf L. Chapter 26. Skin and nail changes. In: Brighton D, Woods M (eds). The Royal Marsden Hospital Handbook ofCancer Chemotherapy a guide for the multidisciplinary team. Edinburgh, Elsevier Churchill Livingstone, 2005.

25. Stephens M. Chapter 29. Pulmonary effects. In: Brighton D, Woods M (eds). The Royal Marsden Hospital Handbook ofCancer Chemotherapy a guide for the multidisciplinary team. Edinburgh, Elsevier Churchill Livingstone, 2005.



Further resources

British Oncology Pharmacy Association. Position statement on safe practice and the pharmaceutical care ofpatients receiving oral anti-cancer chemotherapy. London, BOPA, 2004. Available from: http://www.bopawebsite.org/publications/docs/position-statements (accessed 29 January 2014).

Department of Health. Reference guide to consent for examination or treatment, second edition 2009. London,DH, 2009.

El-Saghir N, Otrock Z, Mufarrij A et al. Dexrazoxane for anthracycline extravasation and GM-CSF for skin ulceration and

wound healing. Lancet Oncol2004; 5: 320-1. Goodin S. Safe handling of oral chemo agents in community settings. Pharmacy Times 2007 (Sep 1). Available from:

http://www.pharmacytimes.com/publications/issue/2007/2007-09/2007-09-6789 (accessed 29 January 2014). Griffin E. Safety considerations and safe handling of oral chemotherapy agents. Clin J Oncol Nurs2003; 7(6 Suppl): 25-9. Langer SW, Sehested M, Jensen PB. Treatment of anthracycline extravasation with dexrazoxane. Clin Cancer Res2000;

6: 3680-6. Nursing and Midwifery Council. The code: Standards of conduct, performance and ethics for nurses and midwives.

London, NMC, 2008. Rickard CM, Webster J, Wallis MC et al. Routine versus clinically indicated replacement of peripheral intravenous

catheters: a randomised controlled equivalence trial. Lancet2012; 380: 1066-74. Royal College of Nursing. Standards for infusion therapy. The RCN IV Therapy Forum. 3rd edition. London, RCN, 2010. Schulmeister L. Chapter 18. Antineoplastic therapy. In: Infusion Nurses Society, Alexander M, Corrigan A et al (eds).

Infusion Nursing. 3rd Edition. Philadelphia, Saunders Elsevier, 2009. Sewell G, Summerhayes M, Stanley A. Administration of chemotherapy. In: Allwood M, Stanley A, Wright P (eds). The

Cytotoxics Handbook. 4th edition. Oxford, Radcliffe Medical Press, 2002. Toft B. External Inquiry into the adverse incident that occurred at Queens Medical Centre, Nottingham, 4th January

2001. London, Department of Health, 2001. Vidall C, Roe H, Dougherty L et al. Dexrazoxane: a management option for anthracycline extravasations. Br J Nurs2013;

22: S6 -12.


21/186February 201420

Nursing implications of drug side effects8,20-25

These are ordered to provide the following:

Patient education

Observations/assessment

Monitoring Action

Haematological toxicity

1 Anaemia encourage good dietary intake, eg, food high in iron such as liver or broccoli/spinach observations for pallor, dizziness, shortness of breath regular FBC

blood transfusion usually packed cells administer erythropoietin as appropriate

2 Leucopenia

encourage meticulous hand hygiene in staff, patients and carers teach patient to recognise early signs of infection and report give chemotherapy alert card to ensure immediate attention at A&E department prevent exposure to adults or children with known infection close observation of patient on steroids take regular swabs and specimens if at risk regular monitoring of white blood cells

administer prophylactic granulyte colony-stimulating factor (GCSF) administer antibiotics and GCSF as required ensure appropriate isolation when WBC very low

3 Thrombocytopenia

warn patient to avoid physical injury avoid use of razor (use electric) avoid IM injections advise use of soft toothbrush teach patient how to recognise early signs and report

avoid drugs that interfere with platelet function, eg, aspirin, alcohol observation for bleeding including petechiae, haematuria regular platelet count administer platelet transfusion

4 Haemorrhagic tendency teach patient to watch for signs of bleeding, epistaxis, haematuria, bruising eliminate other reasons for bleeding, eg, low platelet count

5 Infection/sepsis

explain possibility to patient

give advice about how to prevent infection, recognise signs and symptoms and when to call for advice give chemotherapy alert card to ensure immediate attention at A&E department administer antibiotics within 1 hr of assessment ensure appropriate isolation if required



Gastrointestinal toxicity

6 Stomatitis

advise patient to avoid extremely hot and cold food, heavy spices and citrus fruits, alcohol and smoking regular observation of entire mouth using an oral assessment tool where appropriate check for fungal infections regular mouth washes, every 2-3 hrs and always after meals

soft diet if severe administer analgesics and/or antifungals administer barrier preparation (eg, sucralfate or Gelclair) for local relief

7 Taste aberration (dysgeusia)(i) At time of treatment

offer strongly flavoured sweets during injection(ii) At other times

provide dietary advice advise sipping drinks/chewing gum/sweets

concentrate on foods that taste good sharp tasting drinks may be refreshing

8 Anorexia

encourage meals early in the day as better tolerated advise patient to try small frequent meals consider how food is presented determine dietary habits from nursing history weigh patient regularly offer food supplements provide artificial saliva, if due to dry mouth

refer to dietician

9 Dyspepsia

educate patient administer medications (PPIs, antacids) as indicated

10 Nausea and vomiting

inform patient of what to expect and when advise patient to try dry crackers for nausea suggest patient try distraction, meditation, relaxation, acupressure bands or acupuncture

consider patient preference regarding techniques prior to procedure administer antiemetics prior to chemotherapy and assess effectiveness for highly emetogenic drugs ensure appropriate antiemetics administered pre-SACT and then

regularly, for at least three days after each course maintain fluids and observe for electrolyte imbalance

11 Constipation

warn patient of possibility encourage diet high in fibre encourage fluids provide prophylactic laxatives


23/186February 201422

12 Diarrhoea

warn patient of possibility advise a low roughage diet suggest good perianal hygiene (NB, anal fistulae are more common in immunosuppressed patients) observe for signs of dehydration and electrolyte imbalance provide/administer antidiarrhoea agents



Skin toxicity

13 Venous discolouration

explain possibility to patient reassure patient it is temporary

14 Venous/injection site pain

administer injection slowly with frequent flushes of NS whenever pain occurs always distinguish vein pain from extravasation dilute injection further (if pharmaceutically acceptable) use local heat to aid vasodilation suggest CVAD insertion if pain is difficult to tolerate during infusion

15 Nail discolouration and ridging explain possibility to patient reassure patient it is temporary

16 Skin pigmentation explain reason to patient reassure patient it is temporary advise against prolonged exposure to bright sunlight

17 Phlebitis

(i) Chemical administer drugs with NS flushes administer drugs slowly use large vein with good blood flow use small gauge needle

apply local heat or glyceryl trinitrate patch to increase vasodilation(ii) Thrombophlebitis

inform patient of possibility and that it is temporary apply symptomatic relief (heat/cold) use heparinoid or steroid cream suggest application of anti-inflammatory cream or gel, eg, ibuprofen

18 Flushing(i) If a local flush along vein in arm at time of administration

advise patient that it is temporary

administer hydrocortisone injection/apply cream(ii) If body flushing at time of injection reassure patient that it is temporary slow drug administration

19 Dermatitis/rash inform patient of possibility observe for changes or pain (? shingles) seek dermatology opinion administer antihistamine IV or orally as required apply calamine or similar


25/186February 201424

20 Palmar plantar erythrodysaesthesia (PPE)

advise patient to protect skin from sun encourage and apply greasy emollient to ensure skin is kept supple observe severity and administer pyridoxine administer antibiotics as prescribed

21 Pruritis

educate patient offer antihistamines

22 Erythema multiforme/Stevens-Johnson syndrome/toxic epidermal necrolysis (TEN)

discontinue any medication that could be responsible correct fluid and electrolyte imbalance and nutritional deficits provide analgesia, physiotherapy and wound dressings administer antibiotics for secondary infection

23 Alopecia

explain possibility to patient and advise degree of hair loss provide patient an opportunity to discuss reassure patient that hair will grow back order wig before hair loss encourage patient to cut long hair to prevent the weight pulling on roots advise on hair care frequency of washing, use of a neutral pH shampoo, use of brushes and comb advise against perms and colourants encourage patient to see own hairdresser for support use scalp hypothermia where appropriate



Organ toxicity

24 Hepatic toxicity/abnormal liver function

observe for signs of jaundice test urine for bilirubin monitor LFTs

25 Cardiac toxicity/cardiac symptoms (chest pain, palpitations, arrhythmias, change in ECG pattern) baseline ECG or multiple-gated aquisition (MUGA) scan before treatment and monitor watch for cumulative effect check when reaching total cumulative dose of drug refer to cardiologist

26 Pulmonary toxicity (dyspnoea, cough, pneumonitis, bronchitis) observe for onset of symptoms shortness of breath, wheezing, etc and report ensure a baseline chest X-ray prior to starting treatment check chest X-ray prior to each treatment

advise anaesthetist before surgery treat infection as required

27 Sexual dysfunction

Female warn of amenorrhoea normally reversible after treatment stops advise patient to continue barrier contraception warn of early menopause/infertility discuss options for future fertilityMale discuss pre-treatment sperm banking

warn about possibility of sterility reassure that changes do not cause impotence

28 Discolouration of urine inform patient of possibility reassure patient that it is temporary

29 Haemorrhagic cystitis if patient is receiving high-dose therapy, test urine for blood increase fluid intake before and after treatment

measure fluid intake and output (for very high doses of drug, patient should be catheterised to ensureaccurate measurement of output; forced diuresis may be necessary) mesna given concurrently will protect bladder mucosa from cyclophosphamide and ifosfamide

30 Nephrotoxicity

monitor renal function before treatment and ascertain baseline EDTA or creatinine clearance test urine for pH alkalinisation may be required during treatment record fluid intake and output during treatment ensure adequate hydration; forced diuresis to maintain output may be necessary


27/186February 201426

31 Tumour lysis syndrome

observe for signs and symptoms (tachypnoea, tachycardia, hypotension, pulmonary oedema) monitor and correct electrolyte levels as necessary administer hydration and monitor fluid balance administer allopurinol or rasburicase

32 Peripheral nerve toxicity (paraesthesia and peripheral sensory neuropathy)

explain to patient symptoms they might experience such as laryngo- or bronchospasm encourage patient to wear hat, scarf and gloves in cold weather and avoid cold drinks for 6 hrs after

drugs such as oxaliplatin observations to determine severity reassure patient symptoms will usually disappear 4-6 weeks after stopping treatment change to drug of lesser toxicity

33 CNS toxicity

(i) Observe for signs of problems neurological assessment

exclude cerebral secondaries(ii) Mood swings depression may occur provide patient an opportunity to talk, along with psychological and emotional support

throughout treatment

34 Pain (headache/myalgia, arthralgia) warn patient of possibility and advise not to take aspirin-based analgesia explain need to report any pain that does not resolve administer analgesia as appropriate



Sensory toxicity

35 Ototoxicity

observe for patient reports of tinnitus (high frequency hearing loss often first symptom) ensure baseline audiology testing prior to treatment refer as appropriate

36 Nasal stuffiness explain to patient that it is transient

37 Photosensitivity

advise use of sunglasses advise avoidance of bright lights reassure patient that it is temporary

38 Eye problems (dry eyes/conjunctivitis/blurred vision) explain possibility to patient

advise who to contact if it should occur


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Metabolic toxicity

39 Hypo/hyperglycaemia

observation for signs dizziness, pallor, sweating, confusion monitor for blood glucose levels provide extra glucose/ensure food available (hypo) administer insulin as required (hyper)

administer certain infusions slowly

40 Hyperuricaemia encourage fluid intake observe urinary output administration of allopurinol

41 Hypo/hypercalcaemia

observation for increased neural and muscular excitability (hypo) administration of calcium (unless this is a required effect) (hypo)

observe for complaints of bone/abdominal pain, polyuria, nausea and vomiting, depression and anxiety(hyper) administration of hydration, bisphosphonates or calcitonin (hyper)

42 Hypomagnesaemia/hypophosphataemia observe for signs and symptoms (nervous system excitability, arrhythmia, muscle cramp) (Mg) administration of magnesium replacements (Mg) observe for muscle dysfunction and weakness, white cell dysfunction and mental status changes

(Phos) administration of IV potassium phosphate (Phos)

43 MAO inhibitor usually only very mild reactions warn patient to watch for reactions with high tyramine containing foods eg, alcohol, cheese,

Marmite.

44 Hypo/hyperkalaemia monitor potassium level observe for signs and symptoms (constipation, fatigue, muscle weakness) (hypo) administration of potassium replacement (mild = oral; more severe = IV) (hypo) observe for malaise, palpitations and muscle weakness (hyper)

administration of calcium; may require haemodialysis

45 Hyper/hypothyroidism

observe for signs and symptoms (fatigue, thin brittle hair and dry skin, weakness, unintentional weightgain) (hypo)

administration of medication, eg, levothyroxine (hypo) observe for tremors, anxiety, irritability, tachycardia and increased sweating and restlessness (hyper) administer antithyroid drugs, beta blockers, may require surgery or radioiodine to treat (hyper)

46 Hyperlipidaemia/hypercholesterolaemia

provide dietary advice

monitor levels may require statins



Other toxicity

47 Gynaecomastia

explain possibility to patient

48 Tumour pain reassure patient that effect will pass

administration of analgesia

49 Jaw pain usually of trigeminal neuralgia type reassure patient that effect will pass administer analgesia

50 Carcinogenesis

offer counselling if this occurs or is likely to occur

51 Flu-like symptoms advise patient of possible symptoms fever, chills, headache advise patient that it is temporary administer prophylactic hydrocortisone

52 Hypersensitivity/anaphylaxis

regular nursing observations during drug administration have appropriate drugs ready if anaphylaxis is a possibility (hydrocortisone, chlorphenamine,

adrenaline) check sensitivity to drug with test doses (particularly if previous reaction) following a

desensitisation protocol

add hydrocortisone cover to drug regimen

53 Fatigue

inform patient of possibility explain when it may occur (may be worse when blood cell count is low 10-14 days after SACT) and how

long it might last advise patient to plan activities and have regular rest periods encourage family/friend involvement

54 Hypo/hypertension

monitor BP administer antihypertensive as prescribed if indicated

55 Reactivation of radiation sites explain possibility to patient


31/186February 201430

List of drug monographs

A Afatinib E Epirubicin Panitumumab

Aflibercept Eribulin Pazopanib

Aldesleukin Erlotinib Pemetrexed

Alemtuzumab Estramustine Pentostatin

Arsenic trioxide Etoposide Pertuzumab

Asparaginase Etoposide phosphate Pixantrone

Axitinib Everolimus Pomalidomide

Azacitidine F Fludarabine Ponatinib

B Bendamustine 5-fluorouracil Procarbazine

Bevacizumab Folinic acid R Raltitrexed

Bexarotene G Gefitinib Regorafenib

Bleomycin Gemcitabine Rituximab

Bortezomib H Hydroxycarbamide RuxolitinibBosutinib I Idarubicin S Sorafenib

Brentuximab vedotin Ifosfamide Streptozocin

Busulfan Imatinib Sunitinib

C Cabazitaxel Interferon alfa T Tegafur/gimeracil/oteracil

Capecitabine Ipilimumab Temozolomide

Carboplatin Irinotecan Temsirolimus

Cetuximab L Lapatinib Thalidomide

Chlorambucil Lenalidomide Thiotepa

Cisplatin Lomustine TioguanineCladribine M Melphalan Topotecan

Clofarabine Mercaptopurine Trabectedin

Crizotinib Mesna Trastuzumab

Cyclophosphamide Methotrexate Trastuzumab emtansine

Cytarabine Mifamurtide Treosulfan

D Dacarbazine Mitomycin Tretinoin

Dactinomycin Mitotane V Vandetanib

Dasatinib Mitoxantrone Vemurafenib

Daunorubicin liposomal N Nelarabine Vinblastine

Daunorubicin non-liposomal Nilotinib Vincristine

Decitabine O Ofatumumab Vindesine

Docetaxel Oxaliplatin Vinflunine

Doxorubicin liposomal P Paclitaxel albumin Vinorelbine

Doxorubicin non-liposomal Paclitaxel non-albumin Vismodegib

The Yellow Card Reporting scheme is in place to help the Medicines and Healthcare products Regulatory

Agency (MHRA) monitor the safety of medicines and vaccines in the market.

If you suspect an adverse reaction that may be related to one or more drugs, please complete a Yellow Card.

These can be found in the BNF, MIMS or online at yellowcard.mhra.gov.uk


32/186

A

Guide to frequency of side effects

Very common(1/10)Common (1/100 to



AFATINIBGeneric name Afatinib

Trade name Giotrif

Drug action EGFR tyrosine kinase inhibitor.

Specificinformation

Afatinib is a substrate of P-gp. P-gp inhibitors or inducers could affect exposure toafatinib and dose adjustments may be required.

Methods ofadministration

Oral. Tablets should be taken on an empty stomach. Food should not be consumedfor at least 3 hrs before and at least 1 hr after taking the dose. For patients withswallowing difficulties, the tablets may be dropped in 100ml of non-carbonatedwater and stirred occasionally until dispersed (this may take up to 15 mins), thendrunk immediately. The dispersion can also be administered through a gastric tube.

Side effects Immediate Short-term Long-term

Very common None selected* Anorexia 8 , stomatitis 6 ,diarrhoea 12 , skin reactions(rash, dermatitis acneiform,pruritus, dry skin) 19 21 ,

epistaxis 4

Paronychia

Common None selected* Dyspepsia 9 , dysgeusia 7 ,dehydration, cystitis,conjunctivitis 38 , dry eye 38 ,rhinorrhoea, fever, musclespasm, cheilitis, increasedALT and ALP 25 ,hypokalaemia 44

PPE 20 , renal impairment 30 ,weight loss 8

Uncommon None selected* Keratitis ILD 26

Rare None selected* None selected* None selected*

Very rare None selected* None selected* None selected*

Unknown None selected* None selected* None selected*

Nursing implications ( 1 2 3 etc) see pages 20-29. *None selected for the purposes of this handbook


34/186February 201432

AFLIBERCEPTGeneric name Aflibercept

Trade name Zaltrap

Drug action Blocks the activation of VEGF receptors, inhibiting the growth of new blood vesselsto the tumour.

Specific

information

Check BP and proteinuria before each dose.


IV infusion over 1 hr, using an infusion set containing a 0.2 micron filter.


Very common None selected* Infections 5 , leucopenia 2 ,neutropenia,thrombocytopenia 3 ,headache 34 ,hypertension 54 ,haemorrhage 4 ,

dyspnoea 26 , PPE 20 ,proteinuria, diarrhoea 12

Stomatitis 6 , anorexia 8 ,weight loss, dysphonia,increased AST and ALT 24 ,increased serum creatinine,asthenia

Common Hypersensitivity Neutropenic infections/sepsis 5 , UTI,nasopharyngitis

Fistula, dehydration, arterialand venousthromboembolism,oropharyngeal pain,rhinorrhoea, skinhyperpigmentation 16

Uncommon None selected* GI perforation, impairedwound healing

PRES, nephrotic syndrome,thrombotic microangiopathy

Rare None selected* None selected* None selected*Very rare None selected* None selected* None selected*





ALDESLEUKINGeneric name Aldesleukin, interleukin-2, IL-2

Trade name Proleukin

Drug action Immunomodulator. Mechanism not completely understood.

Specificinformation

May cause potentially fatal capillary leak syndrome which is associated withhypotension, pulmonary oedema and reduced organ perfusion. Careful monitoring

of circulatory and respiratory function is required. Frequency and severity of theseside effects are lower with SC administration than with IV infusion.May exacerbate disease symptoms in patients with unrecognised or untreated CNSmetastases.May exacerbate effusions from serosal surfaces; consider treatment beforeinitiation of therapy.Should be discontinued in patients developing severe lethargy or somnolence;continued administration may result in coma.Pre-existing bacterial infections should be treated prior to initiation of aldesleukin.Toxicities associated with aldesleukin may be exacerbated by concurrent bacterialinfections.

Possible disturbances in glucose metabolism; monitor blood glucose.Perform pre-treatment chest X-rays and ECG.May exacerbate pre-existing autoimmune disease.The solution may be slightly yellow.


SC injection; or IV infusion in 500ml D5W with 0.1% human albumin solution.


Very common Erythema 19 , rash(including exfoliativedermatitis) 19 ,

injection sitereactions 14 , fever,chills, malaise,asthenia/fatigue 53 ,pruritus 21 , sweating

Anxiety 33 , confusion 33 ,depression, insomnia,headache 34 , dizziness,

paraesthesia,somnolence 33 ,dyspnoea 26 , cough 26 ,nausea and vomiting 10 ,diarrhoea 12 , anorexia 8 ,stomatitis 6 ,hypotension 54 , tachycardia;chest pain (includingangina) 25 , oliguria, weightchanges

Anaemia 1 ,thrombocytopenia 3 ,increased serum urea and

creatinine,hypothyroidism 45

Common

(continued onfollowing page)

Phlebitis 17 ,hypothermia Constipation11 , pulmonaryoedema 26 , pleural

effusions, hypoxia,haemoptysis, epistaxis,rhinitis, cyanosis,cardiovascular disorders(including heart failure),irritability, agitation,hallucinations,musculoskeletal pain 34 ,conjunctivitis, dysphagia,

dyspepsia, GI haemorrhage,ascites, gastritis, RTI 5 ,acidosis, hyperglycaemia 39 ,hypocalcaemia 41 ,

Leucopenia 2 , eosinophilia,hypertension 54 ,coagulopathy, arrhythmia,neuropathy, increased LFTsand LDH, hepatomegaly orhepatosplenomegaly 24 ,haematuria,hyperthyroidism 45


36/186February 201434

Common

(Aldesleukinside effectscontinued fromprevious page)

hyperkalaemia 44 ,dehydration, neuropathy,syncope, speech disorders,ageusia, lethargy,hypertension 54 ,haematuria, renal failure 30 ,anuria, alopecia 23 ,mucositis 6

Uncommon Hypersensitivity 52 ,thrombosis,haemorrhage

Hypoglycaemia, coma,seizures, paralysis,myasthenia, pancreatitis,intestinal obstruction, GIperforation, cholecystitis,vitiligo, angioedema,myopathy, myositis

Neutropenia 2 , liver failurewith fatal outcome 24

Rare Anaphylaxis 52 ,pulmonary embolism,ARDS

Optic nerve disorder,vesiculobullous rash,Stevens-Johnson

syndrome 22

Agranulocytosis, diabetes,activation of Crohns disease






ALEMTUZUMABGeneric name Alemtuzumab

Trade name MabCampath

Drug action Monoclonal antibody specific for the CD52 antigen expressed on B and Tlymphocytes.

Specific

information

No longer licensed in the UK but available on a named-patient basis.

Administered in escalating doses during first week: 3mg on day 1, 10mg on day 2and 30mg on day 3. Standard dose is then 30mg 3 times weekly on alternate days.If acute moderate to severe adverse reactions occur at either the 3mg or 10mg doselevels, then those doses should be repeated daily until they are well tolerated beforefurther dose escalation is attempted.If therapy is withheld for more than 7 days, gradual dose escalation is necessary.Patients should be premedicated with oral or IV steroids, an antihistamine andanalgesic 30-60 mins prior to each infusion during dose escalation and as clinicallyindicated thereafter. Since prolonged lymphocyte depletion results from treatment,prophylaxis against Pneumocystis jirovecipneumonia (eg, twice-daily co-trimoxazole3 times weekly) and an antiviral should be initiated and continued until CD4+ count

has recovered. Any blood products needed should be irradiated to prevent GvHD.Methods ofadministration

IV infusion over 2 hrs in 100ml NS or D5W.


Very common Infusion-relatedreactions (fever,hypotension, chills,rash) 21

Rash 19 , nausea,dyspnoea 26 , fatigue 53 ,CMV infection 5

BMD 1 2 3

Common Hypersensitivity/anaphylaxis 52

Pruritus 21 , vomiting 10 ,diarrhoea 12 ,constipation 11 ,bronchospasm, back pain,chest pain, stomatitis 6 ,myalgia 34 , headache 34 ,confusion 33 , anxiety,somnolence, depression,insomnia, tremor, dizziness,GI haemorrhage

Hypertension 54 ,tachycardia 25 , flushing 18 ,palpitations, hyponatraemia,hypocalcaemia 41 ,dehydration

Uncommon None selected* Ageusia 7 None selected*






38/186February 201436

ARSENIC TRIOXIDEGeneric name Arsenic trioxide

Trade name Trisenox

Drug action Not completely understood. Induces DNA fragmentation and degradation.

Specificinformation

Induction treatment is given daily for a maximum of 50 doses. Consolidation therapyshould begin 3-4 weeks later.

Potentially fatal differentiation syndrome can occur, which is characterised by fever,dyspnoea, weight gain, lung infiltrates, pleural or pericardial effusions andleucocytosis. This requires immediate treatment with high-dose steroids(eg, dexamethasone 10mg IV twice daily).Can cause QT prolongation and complete AV block.Caution is advised when coadministered with other drugs known to cause QTprolongation (eg, macrolide antibiotics, the antipsychotic thioridazine), or thoseknown to cause hypokalaemia or hypomagnesaemia. Prior to initiating therapy, a12-lead ECG must be performed and serum electrolytes (potassium, calcium, andmagnesium) and creatinine must be assessed.Pre-existing electrolyte abnormalities must be corrected and, if possible, drugs that

are known to cause QT prolongation must be discontinued.Methods ofadministration

IV infusion over 1-2 hrs in 100-250ml NS or D5W. May be extended to 4 hrs ifvasomotor reactions (tachycardia) are observed.


Very common Tachycardia 25 Hyperglycaemia 39 ,hypokalaemia 44 ,hypomagnesaemia 42 ,differentiation syndrome(see Specific information),dyspnoea 26 , fatigue 53 ,

fever, paraesthesia,dizziness, headache 34 ,nausea and vomiting 10 ,diarrhoea 12 , pruritus, rash,myalgia, oedema, pain

ECG abnormalities 25 ,increased ALT and AST 24

Common Hypotension 54 Arthralgia 34 , bone pain 34 ,pleural effusion 26

BMD 1 2 3 ,hyperbilirubinaemia, weightgain

Uncommon None selected* None selected* None selected*



Unknown None selected* None selected* Pneumonitis 26




ASPARAGINASEGeneric name Asparaginase, crisantaspase

Trade name Erwinase

Drug action An enzyme that breaks down exogenous asparagine that leukaemic cells dependupon for survival.

Specific

information

Treatment may be preceded by an intradermal test dose. Asparaginase-induced

pancreatic dysfunction may cause hyperglycaemia which may be detected by urineor blood glucose monitoring.


Given by IV, IM or SC injection.Avoid froth formation due to excessive or vigorous shaking. The solution should berejected if there are any visible particles due to excessive shaking.The solution should be administered within 15 mins of reconstitution. If a delay ofmore than 15 mins between reconstitution and administration is unavoidable, thesolution should be withdrawn into a glass or polypropylene syringe for the period ofthe delay. The solution should then be used within 8 hrs.Daily clotting screen is necessary owing to the potential for clotting derangement.

Side effects Immediate Short-term Long-termVery common None selected* Coagulation abnormalities None selected*

Common Hypersensitivity (eg,urticaria, fever,aches) 52 ,dyspnoea 26

Increased serum amylasesand lipase 24

Hepatic impairment(increased LFTs andcholesterol, liver toxicity) 24 ,acute pancreatitis,diarrhoea 12 , CNS toxicity(lethargy, depression,drowsiness, seizures,coma) 33

Uncommon Anaphylaxis 52 None selected* None selected*Rare None selected* None selected* None selected*





40/186February 201438

AXITINIBGeneric name Axitinib

Trade name Inlyta

Drug action Selective inhibitor of VEGF receptors 1, 2 and 3.

Specificinformation

Axitinib is metabolised in the liver by cytochrome P450 enzymes. Drugs that arepotent inhibitors or inducers of these enzymes should be avoided.


Oral. Tablets should be swallowed whole, with or without food.


Very common None selected* Dysgeusia 7 , headache 34 ,haemorrhage 4 ,dysphonia 35 , GI upset(diarrhoea 12 ,nausea and vomiting 10 ,constipation 11 ), rash/dryskin 19 , stomatitis 6 ,

proteinuria, fatigue 53 ,mucositis 6

Hypothyroidism 45 ,anorexia/weight loss 8 ,PPE 20 , hypertension 54

Common None selected* Dehydration, dizziness,tinnitus 35 , dyspnoea 26 ,cough, dyspepsia 9 ,flatulence, haemorrhoids,pruritus 21 , erythema 19 ,pain (musculoskeletal,oropharyngeal, extremities,abdominal) 34

Alopecia 23 , increased lipaseand LFTs 24 , embolic andthrombotic events, renalfailure 30 , increased TSH,anaemia 1 ,thrombocytopenia 3

Uncommon None selected* None selected* Polycythaemia, neutropenia,leucopenia 2 ,hyp