Transcript All you need to know about Chemotherapy.

All you need to know
about Chemotherapy.
Lynne Cormode
What is Chemotherapy?
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Systemic treatment against malignant cells to try
and prevent growth, invasion, metastasis and
eventual death of patients.
Initially discovered after WW1 when soldiers
exposed to nitrogen mustard were observed to
have had a improvement in solid tumour size.
Chemotherapy Intent / Terms
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Adjuvant
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To reduce cancer load thereby
improving symptoms and
prognosis
Radical
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To down stage tumour prior to
surgery or radical treatment
Palliative
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To reduce cancer recurrence
Neo-Adjuvant
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Curative treatment
Concomitant
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Combined modality treatment
(Chemo/radiotherapy)
Regime
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Cycle
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Single / Combination Drugs
Varies from weekly to 12
weekly
Dose
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Body surface area i.e. mg/m2
(Dubois + Dubois)
Renal excretion i.e. AUC (Area
under the curve)
Chemotherapy Forms / Types
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Oral
Intravenous
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Locally
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Bolus / Infusional
Central / Peripheral
Intratheccal
Intraperitoneal / Intravesical
Topical
Intra-arterial (limb perfusion)
Subcutaneous or
Intramuscular
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Classic chemotherapy
Immunotherapy
Biological / Molecular
targeted therapy
Modes of Action - General
Inhibition of cell multiplication via
 Macromolecular synthesis and function i.e. DNA /
RNA / Proteins
 Cytoplasmic signalling
 Cell membrane receptor synthesis, expression and
function
 Cellular environment
The Cell Cycle
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Interphase
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G1 (presysnthesis gap)
S (synthesis of DNA)
G2 (postsynthesis gap)
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Mitosis
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M (cell division)
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Prophase
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Metaphase
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Microtubles align chromosomes
Centromeres halfway between spindle
poles
Anaphase
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Sister chromatids condense
Mitotic spindle assembles
Nuclear envelope breaks down
Separation of sister chromatids at
centromere moving towards poles
Cytokinesis (cell division) starts
Telophase
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Nuclear membranes reforms
Chromosomes become extended
Cytokinesis completes
Traditional Chemotherapy Classes
ANTIMETABOLITES
TAXANES
PODOFYLOTOXINS
ANTIMICROTUBULE
AGENTS
CHEMOTHERAPY
VINCA ALKALOIDS
ANTITUMOUR
ANTIBIOTICS
ANTRACYCLINES
CAMPTOTHECINES
ALKYLATING
AGENTS
NITROSOUREAS
PLATINUM DRUGS
Antimetabolites
nucleoside analogues / antagonists
FOLIC ACID
Methotrexate inhibits DHFR
PURINES
Guanine Adenine
TETRAHYDROFOLIC ACID
PYRIMIDINES
Cytosine Thymine Uracil
5FU
Capecitabine
Cytarabine
Mercaptopurine
Azathioprine
Fludarabine
NUCLEOTIDES
DNA REPLICATION
inhibit
Thymidylate synthase
Antitumour Antibiotics
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Topoisomerases are essential enzymes that maintain the
topology of DNA. Inhibtion interferes with both
transcription and replication of DNA by upsetting
proper DNA supercoiling.
Cell cycle specfic – G1 and S phase
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Type I topoisomerase inhibitors,
Camptothecins (Irinotecan, Topotecan)
Type II topoisomerase inhibitors,
Epipodopyllinotoxins (Etoposide);
Antracyclines (Doxorubicin, Daunorubicin) – also induce O2
free radicals that break DNA strands inhibiting replication
Others include Actinomycin D, Mitomycin C, Bleomycin
Antimicrotubule Agents
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Prevent microtubule function therefore
preventing the separation of chromatids.
Cell cycle dependant – M (anaphase)
Taxanes (Paclitaxel; Docetaxel) – causes
hyperstabilisation of microtubules
 Vinca Alkaloids (Vincristine, Vinblastine,
Vinorelbine) – inhibits the assembly of tubulin into
microtubules
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Alkylating agents
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Ability to alkylate many nucleophilic function
groups causing the formation of covalent bonds
(cross linking of DNA)
Non cell cycle specific
Platinum drugs (Oxaliplatin, Cisplatin, Carboplatin)
– renally excreted
 Nitroureas (Carmustine, Lomustine, Semustine)
– highly lipid soluble i.e. cross BBB
 Others Cyclophosphamide, Dacarbazine,
Procarbazine, Melphalan, Busulphan, Chlorambucil.
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Hormones / Cytokines
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Prednisolone / Dexamethasone
Tamoxifen
Aromatase Inhibitors (Letrozole, Anastrozole)
Gonadotropin releasing hormone agonists
(Zoladex)
Interferon alpha
Monoclonal Antibodies
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Designed to target highly expressed tumour specific
antigens thereby increasing the immune response to the
tumour cell.
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Rituximab (CD20)
Cetuximab (Epidermal Growth Factor Receptor 1)
Transtuzumab (Human Epidermal growth factor Receptor 2)
Bevacizumab (Vascular Endothelial Growth Factor)
Tyrosine Kinase Inhibitors
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Imatinib (Philadelphia chromosome, Bcr-Abl TKI)
Erlotinib (EGFR inhibitor)
Sunitinib (multiple receptor inhibitors inc VEGFR, PDGFR)
Chemotherapy Toxicities 1
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Bone Marrow
Suppression
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Skin / Hair
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Neutropenia
Anaemia
Thrombocytopenia
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GI
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Nausea / Vomiting
Mucositis
Reproductive
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Palmar plantar
erythodysthesia
Sun sensitivity
Extravasation
Rashes
Alopecia (scalp cooling)
Nephrotoxicity
Hepatic toxicity
Chemotherapy Toxicities 2
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Neurotoxicity
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Cardiac toxicity
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Peripheral neuropathy
Ototoxicity
Constipation
Coronary vasospasm
Reduced LVEF
Bladder toxicity
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Haemorrhagic cystitis
Practical Issues
Ward admissions
 Neutropenic sepsis
 Symptomatic
myelosupression
 Dehydration
 Cardiac events
 Extravasations
 Anaphylactoid reactions
Chemotherapy spillage
policy