Chemotherapy

Dr Gareth Noble (and Dr Sue Jordan)

Lecture dedicated to Bridie Joyce (1952-2004)

“Me, I m 3 years from diagnosis and going
strong. Hoping to be in the 15% of Stage 3c
that at least make it to 5 years!”

A patient with ovarian cancer

Aims
 What is cancer?
 What are the treatment
options?
 How do they work?
 What are the side
effects?
 Patient management
What is cancer?
 Cancer is a whole-body disease, in which abnormal
forms of the body's cells divide, multiply and spread,
uncontrolled by normal regulators.
 Malignant neoplasms defined as:
 Uncontrolled proliferation
 Local invasiveness
 Metastasis
 Changes in some aspects of the original cell
morphology/function
What are the treatment options?
Treatments may be directed at:
 cure, palliation or prolonging life.

 Chemotherapy:
 inhibit rate of growth or kill cancerous cells
 Not specific – need to target the accelerated cell division
that distinguishes cancer cells from normal cells
Drugs prescribed to treat cancer include:
 Cytotoxics – main focus of the lecture
 Immunological therapies:
 immunosuppressants, such as corticosteroids;
monoclonal antibodies, rituximab, alemtuzumab;
interferon alfa
 Hormones and hormone antagonists:
 important in treatment of breast, uterine and
prostate malignancies. E.g. anti-oestrogen
treatments, such as tamoxifen, anastrozole
 Cytotoxic drugs
 damage actively dividing cells.

 However, they are unable to destroy any

malignant cells which are ‘resting’.
 If these become active later, the immune
system often cannot eliminate them.
Cell Cycle Overview
 THE CELL CYCLE
ALL DIVIDING CELLS

PHASE SPECIFIC DRUGS

ANTI-METABOLITES
METHOTREXATE RELATIVELY
5 Fu INACTIVE

DNA
REPLICATION M Phase VINCRISTINE
(Doubling) VINELASTINE

ORGANELLES,
RNA, PROTEINS etc. = REST - up to 1year
UNTOUCHED by
DRUGS
NB: Hope - host cells recover 1st
 Therefore, anti-cancer therapy may be
repeated in cycles, to catch any malignant
cells as they emerge from their 'resting' state.

 However, patients who experience severe

adverse drug reactions in early cycles, may
decline further treatments.
 PULSE THERAPY

If rapidly dividing host cells recover in 24 hours but tumour cells

in 36 hours, repeated selective cell death may be achieved by
daily administration of the chemotherapeutic agent.
Interrupted lines indicate potential recovery processes (in
absence of drug).
 EFFECTS of TREATMENT
no treatment

Infrequent treatment - survival + symptoms

Early detection & intensive combination

chemotherapy
Cell death > growth
Assumes no drug resistance and
treatment given before symptoms e.g.
A.L.L., Hodgkins
Early surgery + chemo for 1 year while symptom-free for
remaining cells e.g. ca. breast, rectum
 Cytotoxic drugs are usually divided into:
 Alkylating drugs e.g. cyclophosphamide, chlorambucil
 Cytotoxic antibiotics e.g. doxorubicin, bleomycin
 Mitotic inhibitors: Vinca alkaloids (e.g. vincristine) and
etoposide
 Antimetabolites e.g. methotrexate, cytarabine, cladribine
 Other anti-neoplastic drugs, including: platinum
compounds; taxanes.
Alkylating agents (eg Melphalan)
 MoA: creates robust bonds between strands of DNA
preventing replications and breakages
 Administrations: oral or intravenously
 Indications: myeloma’s and some solid tunours,
used frequently in Rx of Leukaemia’s, lympthoma’s,
and ovarian cancers
 Adverse effects: cytotoxicity
Cytotoxic Antibodies (Dactinomycin)
 MoA: prevents transcription and DNA
replication (ie DNA synthesis)
 Admin: Intravenous
 Indications: mainly used for paediatric
cancers
 Adverse: cytotoxicity, does-dependent
cardiotoxicity (free radial damage)
Mitotic inhibitors (Vincristine)
 MoA: prevents mitosis and division of cells
 Admin: IV or orally depending on the agent
 Indications: acute leukaemias, lymphomas,
some solid tumours
 Adverse: an indiscriminate agent, affects all
cells (normal and cancerous); cytotoxicity;
neurological disturbance (neuropathy, loss of
reflexes)
Antimetabolites (Methotrexate)
 MoA: inhibits DNA synthesis
 Admin: Orally, IV, intramuscularly &
intrathecally.
 Indications: acute lymphoblastic leukaemia,
non-Hogkins lympthoma, skin cancer
 Adverse: Cytotoxicity
 Anti-cancer drugs may be prescribed alone or
together with surgery or radiotherapy.

 Cytotoxic drugs are often prescribed in

combinations to enhance effectiveness and
prevent drug resistance.
 Administration of anti-cancer drugs is guided by
local and national protocols (BNF no.49, Dougherty
& Lister 2004).
 Patients should be fully informed of potential benefits and
side-effects.
 Tablets should never be crushed, and capsules never
opened.

Preparation and administration of intravenous drugs

must be under carefully controlled conditions.
Guidelines on handling cytotoxic drugs:
 Trained personnel should reconstitute cytotoxics;
 Reconstitution should be carried out in designated areas;
 Protective clothing (including gloves) should be worn;
 The eyes should be protected and means of first aid should be
specified;
 Pregnant staff should not handle cytotoxics;
 Adequate care should be taken in the disposal of waste
material, including syringes, containers and absorbent
material.
 Doses are calculated by specialists in relation
to the patient’s condition, therapeutic
regimen, age, liver and kidney function,
weight and (sometimes) height or body
surface area.

 Recording weight and height on drug charts

facilitates surface area calculations.
Adverse effects of cytotoxic drugs
 Malignant cells are similar to normal cells.
Therefore, cytotoxics also kill dividing cells
in healthy tissue, causing severe side-effects.

 Some drugs also cause organ damage.

CELL DIVISION

Rapidly Dividing Cells (Normal)

Fibroblasts
Gut Lining lining of GU tract
Skin Hair Follicles
Germ Cells Embryo
Bone Marrow immune system
Common problems include:

Problem Possible management

Patient non-concordance Minimise adverse effects,

- may cause therapeutic particularly nausea, as much
failure as possible.

Customised patient teaching

plans may help.
Gastro-intestinal disturbance
Emesis Ensure preventive anti-emetic therapy is
administered for acute, delayed and anticipatory
symptoms.

Eliminate unpleasant smells from environment.

Ensure oral hygiene is optimal and ice cubes are

available.
Serve meals at room temperature.
Advise resting for 1-2 hours after meals.

Mobilise gradually. Avoid sudden head

movements, for example when transferring the
patient.
Anorexia Monitor intake.
Offer small frequent meals of patient’s choice.

Separate drinks and fruits from meals by 30-60

minutes, if possible.

Ensure food is available any time patients are hungry.

Offer high-calorie foods, such as cream and whole

milk.

Cold food may be more palatable than hot food.

Bitter taste If patient refuses meat, due
to bitter taste, offer
alternative protein, such as
dairy products.

Plastic cutlery may help.

Oral Mucositis (breakdown of Prevention is more effective than treatment.
lining of mouth and oesophagus) Instigate mouth care at earliest opportunity.
Suggest hourly rinses with water.
Highest risk at 5-10 days after
initiation. Use soft toothbrushes 2-3 times/day.
Paricularly fluorouracil, Avoid abrasive, hot or spicy food, vinegar
methotrexate, doxorubicin and and smoking.
related compounds. Inspect the oral cavity regularly for early
signs of damage.
Folinic acid derivatives, such as Avoid ill-fitting dentures.
calcium folinate, may be prescribed
with methotrexate or fluorouracil. Sucking ice during fluorouracil infusions
may help.
Observe for possible hypersensitivity
responses and pyrexia.
Mucositis of bowel causing Monitor bowel movements and fluid loss.
diarrhoea Check electrolytes.

Ensure perianal area is scrupulously clean.

Avoid enemas, if possible, as they may injure the

bowel wall.

Avoid large meals and foods causing flatulence,

such as beans and cabbage.
Ensure dietary advice does not lead to constipation.

Monitor patient for systemic infection, caused by

gastro-intestinal organisms crossing the damaged
gut wall.
Bone marrow suppression Monitor full blood counts
7-10 days after initiation or regularly. If results are
later with alkylating agents abnormal, doctors may
decide to delay treatment.
Low white cell count/ Monitor for infection, for example, raised
neutropenia. afternoon body temperature.

Severe or life-threatening Ask patient to report any sore throat,

infection may follow. chills, burning urine, cough..
Adopt aseptic techniques.
Recovery usually occurs after
some 21 days. Avoid catheters, where possible
Advise patient to avoid exposure to
infection, particularly days 7-10.

Discuss any associated social isolation.

Monitor possible adverse reactions,

Filgrastim and related ‘colony including gastro-intestinal disturbance,
stimulating factors’ may be muscle pain, painful urination, reactions
prescribed. at injection site, lung damage,
hypersensitivity responses.
Folinic acid derivatives may be
prescribed.
Anaemia Review diet and nutritional
supplements. If erythropoietins
are prescribed, monitor for
possible hypertension.
Low platelet count, Report bruising or bleeding.
causing bruising Monitor stools and urine for
and bleeding. blood.
If shaving is essential, use
electric razors.
Avoid suppositaries, rectal
thermometers, intramuscular
injections if possible.
Fatigue due to disease or Check full blood count.
treatment
Ensure adequate intake.

Advise frequent rests.

Plan activities, including

holidays, if possible.

Further cancers, for example, Life-long cancer surveillance

leukaemia associated with for survivors
alkylating agents
Skin damage
Injuries Pressure area vigilance.

Avoid friction and shearing forces.

Allow extra time for procedures such

as transfer to hoist, care of infusion
sites.

Administer skin care and emollients.

Imparied healing Anticipate poor healing and contact

wound care specialists promptly.
Increased risk of sunburn Advise dark glasses and
covering skin with clothing
and sunscreen during exposure
to direct sunlight.
Hair loss/ alopecia Wash & comb hair very gently.
Alteration of body image
Use wide-tooth combs.
Hair usually returns some 8 weeks
after therapy, but may be of different Silk pillows are suggested.
colour or texture.
Protect hair from the wind.

If hair loss occurs, ensure head

covering is available to prevent
sunburn or excess loss of body heat.

Select a wig of the patient’s own hair

colour, preferably before loss.
Dryness of vagina Refer to specialists. Vaginal
gel may be prescribed to
prevent dyspareunia.
Extravasation from Ensure line is patent by administering another
intravenous lines solution before the drug.

Severe tissue damage, Check site frequently.

requiring plastic surgery, has Ask patients to report any discomfort.
been reported.
Protocols for managing extravasation vary
Doxorubicin, vinca alkaloids with drug administered.
are particularly damaging.
Stop infusion immediately extravasation is
suspected, but leave line in place.

Ensure appropriate antidotes are available.

For some drugs, hyaluronidase may be
required.
Organ damage

Accumulation of uric acid, Ensure uric acid is monitored in

causing kidney damage and venous blood samples.
gout
Report joint or neck pain.
If allopurinol, rasburicase are
prescribed, monitor for possible
side-effects, such as gastro-
intestinal and allergy problems.
Kidney damage Monitor fluid balance and/or
e.g. methotrexate, cisplatin standardised daily weights.

Ensure patient is always well

hydrated.

Recommend daily fluid intake

of 2-3 litres, including several
glasses of water.

Offer a selection of cool, clear

liquids.
Haemorrhagic cystitis Encourage fluids for 24-48 hours
(extremely painful) e.g. after administration.
cyclophophamide and related
drugs If mesna is prescribed, be aware of
possible emetic and other side-
effects.
Heart damage Monitor cardiovascular system,
Dysrhythmia– early. vital signs, breathlessness,
Heart failure– late
e.g. doxorubicin, daunorubicin ECG, if indicated.
Infants and older people most
vulnerable.

Nerve damage Report abdominal pain,

e.g. vincristine, vinblastine, constipation, burning pain,
cisplatin, oxaliplatin numbness or loss of function in
limbs or fingers.

Advise that complete recovery may

take months.
Lung damage Pre-therapy and follow-up
e.g.bleomycin, chest X ray and lung function
doxorubicin, methotrexate, tests.
alkylating agents (rarely)

Infertility/ sterility If the patient’s family is not

Premature menopause considered complete, refer to
specialists promptly regarding
storage of reproductive cells or
tissue.

Hypersensitivity responses, including rashes, fever, chills

and anaphylaxis, are relatively common.
Cautions and contra-indications

 Impaired liver or kidney function may

necessitate dose reduction.

 Dehydration (from vomiting, diarrhoea,

hypercalcaemia) may necessitate
postponement of treatment.
Pregnancy
 Pregnant staff (and those who may be
pregnant) should not handle cytotoxics.
 Patients should be advised to use effective
barrier contraception, if appropriate.
 Many anti-cancer drugs can damage the fetus
or cause miscarriage. If cancer is diagnosed
during pregnancy, the woman is confronted
with very difficult decisions.
 Breastfeeding is contra-indicated.

 Children
 Growth should be monitored and optimum nutrition
encouraged.

 If physical isolation is necessary to reduce exposure

to infection, discuss measures to minimise social
isolation.
 Older patients are more vulnerable to adverse
effects, as they have reduced bone marrow, cardiac
and renal reserves.

 Immunisations may be ineffective. If live vaccines,

such as BCG, are administered, vaccine-related
illness may develop.

 Disposal of patients' body fluids/ secretions should

follow local protocols.
Interactions
 Patients should seek advice before taking any non-
prescription drugs, e.g. cimetidine, aspirin and
alcohol.

 Many non-steroidal anti-inflammatory drugs can

worsen the side-effects of methotrexate.

 Effectiveness of etoposide may be reduced by

St.John’s Wort.
 Anticancer drugs interact with many other
drugs.

 For example, co-administration with other

drugs which adversely affect bone marrow,
such as clozapine, may increase the risk of
neutropenia.
 A MODEL FOR IMMUNITY
MALNUTRITION INFECTIONS
protein fungi
bacterial
IMPAIRED
STRESS
protozoal
DRUGS
im. Sup. IMMUNITY TUMOUR
Cytotoxics
steroids
REACTIVATION
INFECTIONS TB
acute viral shingles
chronic bacterial
chronic protozoal

MALIGNANCY

CHRONIC DISEASE
e.g. RF, diabetes
Theoretical curves describing the probabilities of achieving tumour control and
development of major complications as a function of the dose. A and B represent two
different treatment programs. Treatment B offers a higher probability of tumour control,
but at the cost of a greater likelihood of major complications. The choice between
treatments A and B depends on whether the intent is palliative (A) or curative (B),
whether salvage therapy is available in case of treatment failure, and whether the
anticipated complications are life threatening or irreversible on the one hand or
manageable and reversible on the other. (From Bloomer WD, Hellman S: Normal tissue
responses to radiation therapy. Reprinted by permission of the New England Journal of
Medicine 293:80-83, 1975).
Patient Management Issues
 Need Pt assessment:
 General condition
 Individual response to agents
 Adverse reactions (inc hypersensitivity)
 Use developed guidelines (Protection)
 Review periodic laboratory assessments (ie blood
counts, liver function, bone marrow)
 Pt and family education!
References
 Websites:
 http://www.cancer.org/docroot/ETO/eto_1_3_Chemotherapy_Principl
es.asp (American Cancer Society)
 http://www.hse.gov.uk/press/2003/e03179.htm (Safe Handling Regs)
 http://www.patient.co.uk/showdoc/27000559/ (Patient UK)
 http://www.cancerhelp.org.uk/ (Cancer Research UK)

 Textbooks:
 Applied pharmacology : an introduction to pathophysiology and drug
management for nurses and healthcare professionals / Sylvia Prosser
... [et al.] Call Number:RM301 >APP
 Basic pharmacology for nurses / Bruce D. Clayton, Yvonne N. Stock.
Location:Morriston Library Call Number:QV4 >BAS
 Pharmacology / Humphrey P. Rang ... [et al.] Call Number:RM300
>RAN5