chemotherapy Flashcards
curative treatment
aggressive
neoadjuvant treatment
given before surgery to reduce tumour size
adjuvant treatment
given after surgery or with radiotherapy to clean up
palliative treatment
given to prolong life and comfortability
concomitant treatment
drugs given alongside radiotherapy
cytotoxic chemotherapy
acts on all cells, majority of cancer drugs targeting nucleic acids
combination therapy
targets multiple pathways and reduces toxicity of one class - reduced drug resistance
hormone therapy
removes or blocks hormones that the tumour requires to grow
monoclonal antibodies
trastumozab targets HER2 which is sometimes overexpressed in cancer cells
antibody-drug conjugates
antibody attached to very cytotoxic drug so it is taken straight to the tumour
gastrointestinal side effects of chemotherapy
mucositis - sore, ulcerated mouth/throat, changes in taste/appetite, constipation, diarrhoea, nausea,
mucositis treatment and prevention
analgesics, ice, anti- fungal, good oral hygiene, avoiding floss/alcohol and spicy foods
constipation treatment and prevention
fluids, high fibre diet, laxatives and dose reviews
diarrhoea treatment and prevention
small frequent meals, hydration, antibiotics if >24 hr
- delayed (24hr after chemo) loperamide & ciprofloxacin 250 bd 7/7 if >24 hr
- anticholinergic (+ sweating) = subcut atropine
nausea and vomiting risk factors
females, non-smokers, opioids, age, surgery, hypotension, hypoxaemia, migraines, obesity
nausea and vomiting treatment
- acute - metoclopramide
- delayed - dexamethasone
- breakthrough - 5HT3
- anticipatory - lorazepam
- refractory - levomepromazine
scalp/skin side effects
alopecia, hand/foot syndrome (capecitabine) , papulopustular eruptions (EGFR inhibitors)
scalp/skin side effects treatments
scalp cooling, lanolin, clindamycin, steroids and oral antibiotics
blood side effects
myelosuppression, febrile neutropenia
myelosuppression risk factors
hypotension, COPD, leukaemia, dehydrated, inpatient
blood side effects treatment
low risk - antibiotics
high risk - admission!
short term immunotherapy side effects
colitis, pneumonitis, hepatitis, rashes
long term immunotherapy side effects
cardiac issues, cancers, infertility, hypersensitivity, extravasion
grade 1 hypersensitivity
rash/fever
grade 2 hypersensitivity
flushing, fever, dyspnoea
grade 3 hypersensitivity
bronchospasm, angioedema, hypotension
grade 4 hypersensitivity
anaphylaxis
grade 5 hypersensitivity
death
DNA alkylators MOA
forms aziridinium ion and alkylates N7 of guanine. Aziridinium ion is reformed and alkylates another N7 of guanine - forms DNA crosslinks
DNA alkylators example
cyclophosphamide, pro-drug, activated by CYP450 hydroxylation, acrolein by product formed (Michael acceptor)
DNA alkylators mechanisms of resistance
- increased glutathione and glutathione-s-transferase
- increased excision repair enzymes
- changes in cellular drug uptake
DNA platinating agents MOA
form intrastrand crosslinks in DNA, chlorine ligands displaced in vivo by water, positively charged aquated platinum (II) reacts with biological nucleophiles (N7)
DNA platinating agents example and use
- cisplatin, used for testicular, ovarian, head, neck, lung and bladder cancers
DNA platinating agents mechanisms of resistance
- increased repair mechanism
- increased expression of thiol proteins
topoisomerase inhibitors/DNA intercalators MOA
inhibits topoisomerase II by preventing the fixing of double strand breaks - intercalates into DNA
topoisomerase inhibitors/DNA intercalators examples
anthracyclines - daunorubicin and doxorubicin
topoisomerase inhibitors/DNA intercalators mechanisms of resistance
- increased efflux from a cell
- increased expression of p-glycoprotein
anti-mitotic MOA
microtubule assembly
- binds to free alpha beta tubulin dimers to disrupt balance between polymerisation and depolymerisation
microtubule disassembly
- stabilisation of microtubules
anti-mitotic examples
assembly - vinka alkaloids (vinblastine), from periwinkle plant
disassembly - paclitaxel from yew bark
anti mitotics resistasnce
- over expression of p-glycoprotein
- mutations in tubulin gene
anti-metabolites MOA
5-fdUMP Michael addition with thymidylate synthase and dihydrofolate (during folic acid production) and covalently binds to stop dTMP production
anti-metabolites examples
5-fluoro-deoxyuridine (uracil - like structure)
anti-folates
methotrexate, competitive inhibitor of dihydrofolate reductase
types of modern chemotherapy
PARP inhibitors (ribs) and tyrosine kinase inhibitors (nibs)
PARP inhibitors example
- Olaparib, for ovarian, fallopian and peritoneal cancers with BRCA1/2
discovery of PARP inhibitors
medium throughput screening, benzyl phthalazinone core moderately potent antagonist of PARP1, cyclopropylamide increased oral bioavailability
PARP inhibitors MOA
inhibits poly(ADP)ribose polymerase which is used to repair single stranded breaks
tyrosine kinase inhibitor example
imatinib - BCR-ABL kinase inhibitor
sorafenib - BRAF inhibitor
discovery of BCR-ABL kinase inhibitors
identified 2-phenylaminopyrimidines, methyl group increased selectivity and piperidine made it water soluble
tyrosine kinase inhibitors mechanisms of resistance
- mutations in target protein
- upregulation of other pathways
