CYTOTOXIC

CHEMOTHERAPY

AN INTRODUCTION

Introduction

History of Cancer Chemotherapy

Basic Principles of chemotherapy
Routes of administration
Side effects of chemotherapy
Nursing Care of patients receiving
chemotherapy
Safe handling of chemotherapy

Cytotoxic Chemotherapy
Cytotoxic literally translated means toxic to
cells. Hence these drugs are those which kill
cells.
Chemotherapy - the treatment of disease by
the use of chemical substances

History of Cancer
Chemotherapy
1940-1950
Beginnings of the modern era of chemotherapy
traced directly to discovery of nitrogen
mustard (chemical warfare agent) as an
effective treatment for cancer.
Autopsy observations of people exposed to
mustard gas revealed lymphoid and myeloid
suppression

History of Cancer
Chemotherapy
1940-1950
Goodman and Gilman reasoned that this agent
could be used to treat lymphoma, since
lymphoma is a tumour of lymphoid cells.
Set up an animal model, establishing
lymphoma in mice and treated them with
mustard gas.

History of Cancer
Chemotherapy
1940-1950
In collaboration with a thoracic surgeon, they injected
a related agent (mustine) into a patient with nonhodgkins lymphoma and observed a dramatic
reduction in the patients tumour mass.
Although this effect only lasted a few weeks, this was
the first step to the realisation that cancer could be
treated with pharmacological agents

History of Cancer
Chemotherapy
Combination chemotherapy 1965
Cancer cells could conceivably mutate to
become resistant to a single agent, but using
different drugs concurrently would make it
extremely difficult for the tumour to develop
resistance to the combination.
Induced long term remission in children with
ALL.

CANCER CHEMOTHERAPY
Cancer cells have non of the normal self
regulating controls that non malignant cells
have in place.
They have a larger proportion of cells in the
active growing phase (high growth fraction)

BASIC PRINCIPLES
Prevents cancer cells from multiplying,
invading, metastasising and killing patient.
Affects cell multiplication and tumour growth.
Especially affects cells with a rapid rate of
turnover.
Effectively given - marked effect and minimal
toxicity.

CELL CYCLE

ROUTES OF
ADMINISTRATION
Orally e.g. methotrexate
IV
SC
Intrathecal e.g. methotrexate, cytarabine

CELL CYCLE SPECIFIC

VERSUS NON-SPECIFIC
Certain chemotherapy drugs require cells to be
in cycle for activity (i.e. not resting).
Cell Cycle specific - most active against cells
in a specific phase therefore need prolonged
exposure or repeated doses.
Cell Cycle Non-specific - most effective
against actively dividing cells but also
effective in G0.

DOSE AND SCHEDULE

Aim to maximise dose while minimising
toxicity
Only a proportion of cells die within given
treatment therefore repeated doses are used.
CCS - prolonged exposure e.g. continuous
infusion.
CCNS - dose dependant but toxicity increased.

COMBINATION THERAPY

Reduces resistance to drugs

Increased effectiveness
Access to sanctuary sites e.g. lungs, CSF.
Combinations selected to avoid overlapping
toxicity but:
Causes spectrum of adverse effects but
minimises risk of lethal effects.

CONVENTIONAL
CHEMOTHERAPY
Chemotherapy may be used conventionally to:
cure patients
prolong survival
palliative care

ADJUVANT
CHEMOTHERAPY
Adjuvant chemotherapy may be given with
potentially curative treatment:
Surgery e.g. Ca Breast
Radiotherapy e.g. Lymphomas/Leukaemias

NEOADJUVANT THERAPY
Administration of chemotherapy to shrink a
tumour before it is removed surgically.
eg colo rectal cancers and gynaecological Ca

Induction therapy
Therapy given as the primary treatment for a
disease.
eg Leukaemias and Lymphomas

Palliative

Symptom Control i.e pain control when

previous therapy has failed or disease has
relapsed.

SIDE EFFECTS OF
CHEMOTHERAPY
Both normal cells and cancer cells multiply
Chemotherapy affects cells with high growth
fraction
Normal tissues with high growth fraction
include:
Bone Marrow, Hair follicles, GI mucosa, Skin.

SIDE EFFECTS contd

Common side effects therefore include:
decreased WBC, RBC and platelets
alopecia
stomatitis and/or mucositis

SIDE EFFECTS contd

Chemotherapydrugs/classes vary in their
ability to cause these and other side effects.
Severity of these side effects also varies
between drugs e.g in relation to the degree of
myelosuppression
Other side effects may be drug or class
specific e.g. anthracyclines and cardiotoxicity.

SIDE EFFECTS contd

Nausea and vomiting is also a side effect
caused by the stimulation of the vomiting
centre in the CNS and stimulation of the
nerves in the GI tract.
Drugs vary in potential of emesis, pattern of
emesis e.g. onset and duration and dose of the
drug e.g. cyclophosphamide.

SIDE EFFECTS contd

Extravasation :
The leakage of intravenous drugs into the
surrounding tissues.
Some chemotherapeutic agents are vesicants these are drugs which have the potential to
cause tissue damage.

NURSING CARE
Explain the procedure of administration, oral ,
iv, s/c
Explain side effects in particular risk of
infection and mouthcare
Assess venous access if IV route of
administration.
Administration of anti-emetics

NURSING CARE contd

Assess anti-emetic regimen, - is it effective?

Nutritional intake
Fluid intake / balance
signs of infection e.g.Hickman line site / BP,
TPR.
Psychological care e.g. altered body image,
diagnosis of life threatening disease, fear of
dying.

SAFE HANDLING
Essential to reduce risks to involved personnel.
Cytotoxic drugs are carcinogenic, mutagenic
and teratogenic.

SAFE HANDLING contd

Potential exposure to staff occurs during:

preparation
administration and changing lines etc
handling of body fluids e.g urine
handling of chemo waste products e.g lines,
medication bottles
spillage / leakage of chemotherapy
transportation

LATE EFFECTS
Infertility
Secondary malignancy
Growth retardation

History of Cancer
Chemotherapy
Targeted Therapy 1990s Present
Molecular and genetic approaches to
understanding cell biology have uncovered
entirely new signalling networks that regulate
cellular activities such as proliferation and
survival.

History of Cancer
Chemotherapy
Monoclonal antibodies
Immune proteins which can be selected to
precisely bind to almost any target.
Derived from mice and available for decades
but when administered to humans caused
allergic reactions.

History of Cancer
Chemotherapy
Monoclonal antibodies
Humanisation of these antibodies
(genetically transforming them to be as similar
to a human antibodies as possible) has allowed
the creation of a new family of highly effective
humanised monoclonal antibodies.

SUMMARY

The potential benefit to the patient of treatment

as an option must always outweigh the toxic
effects.