chemotherapy

what is chemotherapy?

a treatment which leads directly or indirectly to the death of a dividing cell/cancer cell

what is the aim of chemotherapy?

destruction and death of cancer cells with minimal or acceptable damage to 'bystander' healthy cells

what are some terms to describe different ways chemotherapy can be given?

- neoadjuvant

- adjuvant

- curative

- synchronous

- palliative

what does neoadjuvant mean?

given before surgery or radiotherapy

what does adjuvant mean?

given after surgery or radiotherapy

what does curative mean?

given standalone

what does synchronous mean?

- also called chemoradiation

- given alongside radiation

what does palliative mean?

- without curative intent

- decrease tumour load and increase life expectancy

which tumours would curative chemotherapy be used for?

childhood:

- ALL

- Wilms Tumour

- Ewings

- rhabdomyosarcoma

- neuroblastoma

adult:

- lymphomas (H + NH)

- teratomas and seminomas

- gestational trophoblastic neoplasm

which tumours would neoadjuvant or adjuvant chemotherapy be used for?

- breast

- bowel

- lung

- stomach/oesophagus

which type of cancers would chemo-radiotherapy be used for?

squamous cell cancers:

- head and neck

- cervical

- oesophagus

- rectal

- anal

what are the 5 main types of traditional cytotoxics?

- alkylating agents

- antimetabolites

- mitotic inhibitors

- anthracyclines

- topoisomerase inhibitors

what is the mechanism of action of alkylating agents? (3)

- cross-link guanine nucleobases in DNA

- strands are unable to uncoil

- DNA cannot replicate so cells cannot divide

what are some limitations of alkylating agents? (2)

- mutagenic and carcinogenic

- non-selective to cancer-cells

what are some examples of alkylating agents? (4)

- platinum compounds - cisplatin, oxaliplatin

- chlorambucil

- cyclophosphamide

what are antimetabolites?

folic acid, purine or pyrimidine analogues

what is the moa of antimetabolites?

they mimic nucleotide precursors Uracil, Thymine, Cytosine, Guanine and Adenine - which inhibits DNA and RNA synthesis

what are some examples of pyrimidine antagonists? (4)

- 5-fluorouracil

- capecitabine

- cytarabine

- gemcitabine

what are some examples of purine antagonists? (5)

- 6-mercaptopurine

- tioguanine

- cladribine

- fludarabine

- dacarbazine

how does folate aid DNA synthesis?

helps with the biosynthesis of purine and pyrimidine bases

how is folate activated?

- intracellular folate is activated by dihydrofolate reductase (DHFR) to dihydrofolate

- dihydrofolate is again activated by DHFR to active folate

what is an example of a folate antagonist?

methotrexate

what are anthracyclines derived from?

streptomyces bacteria

what are the moas of anthracyclines? (5)

- intercalation of replicating DNA

- intercalation of mitochondrial DNA

- inhibitor of topoisomerase II enzyme

- topoisomerase I inhibition

- free radical formation and damage via iron/ferritin pathways

what is the function of topoisomerase enzymes?

unwind supercoiling of DNA to allow replication and transcription

what is a disadvantage of anthracyclines?

very cardiotoxic

what are two examples of anthracyclines?

- daunorubicin

- epirubicin

- doxonrubicin

what is the moa of mitotic inhibitors?

inhibits mitosis by inhibiting microtubule formation

what are the two main classes of mitotic inhibitors?

vinca alkaloids - vincristine, vinblastine, vinorelbine

taxanes - docetaxol, paclitaxel

what are the two types of topoisomerase inhibitors?

topoisomerase I and II inhibitors

what do topoisomerase I inhibitors do?

- work at macro level

- stop the DNA coil from unwrapping

what are two examples of topoisomerase I inhibitors>

- topotecan

- irinotecan

what do topoisomerase II inhibitors do?

- work at micro level

- stop the two DNA strands from separating

what is an example of a topoisomerase II inhibitor?

etoposide

what point in the cell cycle do alkylating agents work?

non-specific

what point in the cell cycle do antimetabolites work?

S-phase

what point in the cell cycle do anthracyclines work?

non-specific

what point in the cell cycle do mitotic inhibitors work?

M-phase

what point in the cell cycle do topoisomerase inhibitors work?

between S and G2 phase

what are some side effects of chemotherapy?

blood - neutropenia

mucous membranes - sore mouth

skin - rashes, breakdown

GI tract - N+V

hair follicles - alopecia

reproductive cells - fertility problems

healing - infection risk