Cancer treatments in palliative care

Clare Warnock

Practice development sister

Weston Park Hospital

Overview of session

• How does cancer treatment work – The difference between normal cells and cancer cells– How cancer treatments work on these differences

• Systemic anticancer therapy– Different types of treatment– How they are given– Side effects

• Radiotherapy– How it works – How it is given– Side effects

The differences between a cancer cell

and a normal cell • Differentiation – what it looks like• Ability to spread – direct and metastatic • Growth

• Healthy cell reproduction – Carefully controlled process– Cell division triggered by the death of a cell– Cell reproduction and cell death carefully balanced

• Different processes act in cancer cells so their reproduction is not constrained by these usual controls

The rate of growth• Doubling time

– Time it takes for a cancer to double in size• 30 times

– One billion cells (marble size)– Can be detected by X- ray or palpation

• 10 more doublings– One trillion– Usually the point at which life cannot be sustained

• For much of its growth cancer is undetectable• The doubling time (rate of growth) for different cancers

varies greatly from hours to years• Cancer growth is often a sustained and constant

process rather than a rapid one

Growth curve for cancer

Limit ofdetection

Lethal limit Treatment

Immune system can

handle

Cure Palliative

Cancer as a chronic disease

• Chronic diseases– Shaped by periods of acute and intensive illness

followed by periods of remission• People with cancer are living for longer with a

chronic, but life threatening, illness• Challenges the portrayal/ perception of cancer • Challenges the concept of “palliative” in relation to

cancer and its treatment• Concept of the “survivor” having increasing

relevance in cancer care

Cancer treatments

• Cancer treatments capitalise on the characteristics of cancer cells

• In particular – more frequent cellular division– poor ability to repair damage compared with normal

cells• Radiotherapy and Chemotherapy are often most

effective when cells are dividing – This is one reason why they have a greater effect on

cancer cells compared with healthy cells

Systemic anti-cancer therapy (SACT)

• Chemotherapy

• Biological therapy

The action of chemotherapy

• Chemotherapy is a systemic treatment– This means it can effect all the cells in the body

• Chemotherapy drugs interfere with the process of cell replication

• Different chemotherapy drugs achieve this is different ways

• Many work at specific stages in the process of cell replication– This is often referred to as the cell cycle

How does anti-cancer therapy work

Genes that promotecell division

(proto-oncogenes)

production of growth

stimulating factors

Tumour suppressor

Genes that controlcell division

production of growth inhibiting

factors

MMMitosisMitosis

SSDNA synthesisDNA synthesis

GG2 2

Later growth phaseLater growth phase

GG11

Early growth phaseEarly growth phase

GG00

Resting Resting phasephase

The cell cycle clockGrowth promotingfactors

Growth inhibitingfactors

Green = chemotherapy action

Yellow = biological therapy action

How does chemotherapy work?

• Some drugs work at specific parts of the cell cycle, others can work at any point

• Actions include– Preventing cell division (M phase) by fusing the old

and new cells together – Inhibiting enzymes involved in DNA synthesis– Interfering directly with DNA

How does biological therapy work

• Targeted therapy

• Range of modes of action– Inhibit the signalling pathway that causes cell

division– Prevent the formation of tumour blood vessels– Prevent the production of particular enzymes

which stop the cell from dividing • All have the effect of slowing or stopping tumour

growth

Examples of targeted therapy

• Tyrosine Kinase Inhibitors (TKI’s) – Erlotinib/Tarceva®

– Sunitinib/Sutent®

– Imatinib/Glivec®

• Monoclonal Antibodies (MAB’s)– Rituximab– Bevacizumab (avastin)

• HER2 positive– Herceptin

The aims of SACT • Maximise the damage to cancer cells • Minimise the damage to healthy cells

• How is this achieved?• Giving combinations of drugs

– Drugs that work in different ways increases cancer cell kill

– Giving drugs with different side effects reduces overall side effect profile

• Cycles of administration – Giving chemotherapy at planned intervals – Increases the chance of catching cells in the

sensitive phase– Allow healthy cells to repair

Intention of treatment• Curative

– Aims to eradicate measurable disease – Treatment often intensive and associated with greater

toxicity – Improved outcomes by maintaining intensity and

avoiding delays in treatment and dose reductions• Palliative

– Aim to extend survival, alleviate disease and improve quality of life

– Careful balance between quality of life and treatment outcomes

• Side effects, duration of response, time in hospital, disruption of ADL’s

Health and safetyReducing exposure to a minimum

• Chemotherapy is mutagenic, teraterogenic and carcinogenic

• Primary routes of exposure– Absorption through skin, inhalation, ingestion– Patients excrete the drugs over the next 7 days

• Provision of protective clothing– Gloves and aprons – universal precautions when handling body fluids

• Guidelines – preparation, handling, disposal and spillages– Pregnancy – don’t handle or administer

chemotherapy

Administration – method and route

• Intravenous– bolus – infusion – infusor (ambulatory chemotherapy)

• Intrathecal• Intramuscular• Intravesical

Oral anticancer therapy

• Increase in oral treatments over past 5 years• Misconception that a tablet isn’t going to cause as many

problems as intravenous– Many have potentially distressing and life threatening side

effects • Self medicating

– Patient information and compliance essential– Risk of patients continuing with treatment when experiencing

side effects • Health and safety issues include: -

– Always wear gloves when handling oral chemotherapy – Never crush tablets or open capsules– Safe storage vital, away from children

Side effects

• The incidence and occurrence of side effects is drug and dose related

• It is essential to know the regime specific facts

Nausea and vomiting

• Acute - occurs within minutes to hours and resolves within 24 hours

• Delayed - 16 to 24 hours post chemotherapy, persists for hours to days

• Anticipatory - conditioned response

• Ematogenic potential– How likely a drug is to cause nausea and vomiting

Nausea and vomiting

• Medium to high ematogenic potential eg cisplatin and doxorubicin

• Antiemetics prescribed as part of the protocol for the regime

– graniestron, ondansetron and apprepitant– IV and oral steroids (dexamethasone)

• lower ematogenic potential ie fluorouracil • “as required” antiemetics prescribed e.g.

domperidone • Encourage patients to report symptoms before next

treatment so we can get the management right

Neutropaenia

• Low count of neutrophils – used as an indicator of infection risk

• Neutrophils ingest and kill bacteria and viruses in circulating blood– Normal range - 2.5 to 6.0 X109/l – Less than 1.0 X 109/l – neutropaenia– Less than 0.5 X 109/l serious risk of bacteraemia

• Normal process of controlling bacterial infection is diminished– can lead to life threatening infections

• When and where to seek support– WPH assessment unit nurse

Neutropaenic sepsis• White blood count of less than 1.0 X 209/l and one of

the following– Oral temp >380c – Any unexplained deterioration in the absence of

fever– HOWEVER – we ask patients to ring if the have a

temperature above 37.5 OR feel unwell• Treatment

– RING WPH and come in for review• Urgent blood test required • Deterioration can be rapid

Thrombocytopaenia

• Low platelets• Increased risk of bleeding

Care issues• Monitor for any signs of bleeding, bruising, petichae • Avoid invasive procedures • Patient information – ring and blood test

– May need platelet transfusion

Altered bowel habit

Diarrhoea• Potentially life threatening complication • Severe diarrhoea may require hospital admission to

prevent dehydration• Anti-diarrhoeal medication – loperamide• If not controlled patient must contact WPH

Constipation• Vinca alkaloids• Exacerbated by graniestron• Risk of paralytic ileus • May need laxatives

Other common side efects

• Sore mouth• Hair loss• Fatigue• Cardiac toxicity – acute and chronic

– NB Capecitabine and 5FU infusor, coronary artery spasm – 999 call

• Peripheral neuropathy• Renal toxicity• Fertility effects

Hand foot syndrome

• Palmar plantar erythrodyesthesia• Incidence increasing due to new drugs• Symptoms:

– dysesthesia, parasthesia in the palms and soles – Swelling on the pads and distal phalanges– Vesicles and desquamation over the pressure areas– Blistering and necrosis– Can be intensely painful and disrupt ADL’s

• Diminishes once treatment has ended

Skin reactions

• Marked skin reactions can occur with some chemotherapy agents particularly TKI’s such as Tarceva

• Patients are advised to use moisturising cream to try and prevent the skin from becoming to dry

• Avoid strong sunlight and use a high SPF sunscreen

• It may appear like acne but it should not be treated with acne medication

• Some patients may require steroids or antibiotics

Radiotherapy

Radiotherapy

• Radiotherapy is a local treatment– Targeted to specific sites in the body

• Radiotherapy uses ionising radiation to damage DNA

• Ionising = radiation that is able to disrupt the chemical structure of the material through which it passes

• It excites cell molecules changing the atomic and molecular structure

Factors affecting radiosensitivity

• Radiotherapy works more effectively for particular types and sites of cancers

• One factor affecting radio-sensitivity is the phase of the cell cycle– The process of cell reproduction

• Tends to work during phases of the cell cycle when DNA synthesis can be disrupted or replication disturbed

– G1, G2, M • It affects all the cells in the treatment site but has a

greater effect on cancer cells – Cancer cells are more likely to be in the cell cycle

The cell cycle

How is it given?

• External beam– Linear accelerator

• Treatment delivered by therapy radiographers• Radiation created by, and remains in, the machine

• Brachytherapy– Sealed and unsealed sources

• Sealed source – radiation is located in the source• Unsealed sources – patient is temporarily radioactive

Linear accelerator

• Successful treatment depends on the therapeutic ratio – optimising the dose to the cancer – minimising damage to normal cells

• Controlling the treatment area– Planning and accurate positioning

Careful positioning

How to achieve the therapeutic ratio

• Fractionation

• Division of the total dose into smaller doses – e.g.60 Gy 30# for a curative regime

• Allows for normal cell repair• Increases chances of catching cells when

sensitive • Allows re-oxygenation of the tumour

• Palliative regimes tend to be shorter and use lower doses

Uses of Radiotherapy in palliative care• Radiotherapy can be for curative or palliative intent

• Palliative treatments include:– Reduction in tumour mass with the intention to

• prolong survival and/or • increase quality of life and/or • symptom management

– Management of bone metastases– Treatment of brain metastases– Oncology emergencies e.g. Spinal cord compression,

SVCO– Fungating lesions– Management of bleeding

Pain and bone metastases • Bone metastases are the most common

secondary site of spread• Most common cause of pain in malignancy• Frequently arise from

– breast, prostate (combined = 80% of incidence)– lung, kidney, thyroid, multiple myeloma,

gastrointestinal• Pain may be due to

– Bone changes– Pathological fracture– Neuropathic pain if presses on adjacent nerve– Spinal cord compression

How external beam radiotherapy works on bone metastases

• Cytotoxic effect on normal bone cells inhibits the release of chemical mediators of pain such as prostaglandins– Some patients get relief in 24 hours

• Effect on cancer cells prevents further bone destruction, reduces tumour size and enables bone resorption– The pain relief effect achieved between 2 and 8

weeks of treatment

Oncology palliative emergencies

• Radiotherapy plays a role in treating and managing symptoms from key palliative emergencies

• Spinal cord compression– Early detection vital as functional outcome of

treatment is related to function on presentation• Superior vena cava obstruction• Brain metastases

Tumour size reduction

• Palliative radiotherapy can be used to reduce size of tumour and actual and/or potential problems – inoperable/ recurrent local tumour or nodal

compression• A higher dose palliation programme may be needed• Patient may have 30 – 45 Gy over 2 – 4 weeks using

multiple fields• Side effects are more likely to occur • Incidence and severity will depend on dose given, site

treated and other patient related factors

Side effects of radiotherapy

• Categorised as systemic and local, acute and chronic (6 months after treatment)

• Local effects are specific to the area being treated• Acute side effects tend to occur within the first 2

weeks of treatment, increase in severity and peak 10 days after treatment completion

• Chronic side effects are usually caused by a decrease in blood supply to the tissue being irradiated leading to fibrosis, stenosis, or necrosis

• Palliative radiotherapy regimes are aimed at inducing fewer side effects (lower total doses, fewer fractions)

Fatigue• Fatigue has been reported as one of the most distressing side

effects of treatment• It is consistently identified as the most common and most

distressing symptom in research into radiotherapy side effects • It increases over the course of radiotherapy and may continue for

months following completion• Important to warn patients it may occur and there are

physiological causes (not them!)

• Interventions include – Rule out other causes, sleep hygiene, maintain activity –

gentle exercise– May not be appropriate for all palliative care needs

Skin reactions

• Skin reactions range from faint erythema to moist desquamation

• Relate to facors inlcuding – Dose, location (skin folds, proximity to skin surface)– Age, general health, smoking

Skin care• Washing skin using mild, unperfumed soap and

warm water– avoid friction - pat skin dry, loose cotton clothing

• During the first stage of a reaction applying moisturising cream can provide relief and prevent deterioration– E45, Oilatum or Diprobase

• Avoid perfumed products• Use an electric razor instead of wet shaving• Protect skin from sun, wind and extreme temperatures• Reactions are greatest at the end of radiotherapy when

the patient has completed treatment • Contact radiotherapy treatment area for advice on

management

Site specific side effects

• The incidence and severity of side effects is dose and treatment site related

• What side effects could patients experience when having radiotherapy to– Brain– Head and neck– Chest– Abdomen and pelvis

The context of treatment

• It is essential to remember that an individuals experience of cancer and its treatment is shaped by contextual factors

Context of treatments

• Previous treatment• Diagnosis• Disease trajectory• Belief about cancer/DXR• Knowledge and

understanding• Relationship with HCP’s• Symptoms• Prognosis

• Home situation• Family and friends• Stage in life• Work and social life• Financial situation• Body image• Past experience• Physical functioning• Other illnesses

Conclusion

• When used appropriately cancer treatments aim to – increase survival, improve symptom management and

quality of life• Preventing, monitoring and managing side

effects are essential if these aims are ot be achieved

• All HCPs play a role in this process• Advice and information is available from WPH

– 0114 226 5000– Nurse practitioner assessment unit – Patient’s consultant team

• Thank you for listening……• Hope you found the journey interesting!