Principles of

chemotherapy
PBL 5.04 Big Dads
What is chemotherapy?
Drugs used to induce apoptosis in cancer cells
Cancer cells proliferate quickly; chemo
interrupts replication at various points in the
cell cycle
Can act systemically (as opposed to radiation
and surgery); useful for metastases
Used to:
- cure/achieve remission
- control growth or spread
- palliate symptoms
Alkylating agents
Prevents reproduction by DNA damage
Attaches an alkyl group onto DNA
Work in all phases of the cell cycle and on many
different cancers (lung, breast, ovary, leukaemia,
lymphoma)
Cell-cycle nonspecific
Altretamine, busulfan, etc.
Antimetabolites
Interfere with DNA and RNA production
Mimics a purine or pyramidine (normal building
blocks of RNA/DNA). Therefore those
substances are not incorporated into DNA
during S phase
Used for leukaemias, breast, ovary and GI
cancers
Cell-cycle specific
5-fluorouracil, 6-mercaptopurine, etc.
Anthracyclines (anti-tumour
antibiotic)
Works thus:
- Inhibits DNA/RNA synthesis by
intercalation
- Inhibits pro-transcription enzymes
- Produces oxygen free radicals that cook
stuff
- Evicts histones! Get outta here!
Can cause permanent heart damage, and
patients are allocated a maximum lifetime dose for
this reason
Mitotic inhibitors
Disrupt microtubules, thus interfering with
mitosis
- taxanes prevent depolymerisation
- vinca alkaloids prevent polymerisation
Cell-cycle specific; M phase
Used in breast, lung, myelomas, lymphomas,
leukaemias
Taxanes: paclitaxel, docetaxel, etc.
Vinca alkaloids: vinblastine, vincristine, etc.
Others
Patient and neoplasm
characteristics
Type of cancer, stage of cancer, particular
mutation, other specific biological traits
General health (comorbidities), fitness, age,
fertility considerations (some drugs better than
others)
Side-effect profile
Response rates (based on research; what
percentage of neoplasms respond to this drug?)
Routes of administration, and
dosage
Narrow therapeutic window; dose and timing
is important
Usually given in combination with other
agents that act at different stages in the cell cycle
- efficacy is enhanced
- can counter development of
resistance
- all act by different mechanisms
- adverse effects are decreased
Routes of administration, and
dosage
Given orally, IV, or via subcutaneous or
intramuscular injection
Can also be applied topically, intraperitoneally,
intrapleurally, or intra-arterially to the vessel
supplying the neoplasm
Given in cycles to allow normal cells to recover
Treatment modalities:
- first/second-line chemotherapy
- adjuvant chemotherapy
- neoadjuvant chemotherapy
Side-effects and management
In general, cell types that proliferate quickly are
susceptible to apoptosis from chemotherapy
Haematopoietic stem cells in the BM;
pancytopenia
Hair follicles (causes alopecia)
GIT cells including mouth, stomach (causing
vomiting, diarrhoea, nausea)
Highly variable
Side-effects may resolve quickly after treatment
but may last for months or years
References
https://en.wikipedia.org/wiki/Chemotherapy
https://www.cancercouncil.com.au/wp-
content/uploads/2014/05/UC-pub-Chemotherapy-CAN708-lo-
res-Aug-2016.pdf
https://www.cancer.org/treatment/treatments-and-side-
effects/treatment-types/chemotherapy/how-chemotherapy-
drugs-work.html
https://www.canteen.org.au/about-cancer/how-is-cancer-
treated/treatments/chemotherapy/
https://old.cancer.org/acs/groups/cid/documents/webcontent/0