13) Cancer Chemotherapy Flashcards
What is the log kill ratio?
Giving treatments that will kill 10^x cancer cells, reducing tumour size
Why is chemotherapy dose fractionated?
To allow normal cells to recover between doses
Tumour cells will recover slower due to damage/mutation to DNA repair genes
Which tumours have high sensitivity to chemotherapy?
Lymphoma, neuroblastoma
Which tumours have low sensitivity to chemotherapy?
Prostate, brain tumours
What are some classes of cytotoxic agents?
Antimetabolites
Alkylating agents
Intercalating agents
Spindle poisons
What is the mechanism of action of alkylating agents?
Covalently bond to nucleophilic target sites on DNA, leading to inter and intra-strand adducts and inhibition of DNA synthesis
What are some intercalating agents?
Anthracyclin, bleomycin
What is the mechanism of action of anthracyclins?
Molecular ring structure that allows them to intercalate between DNA base pairs. Affect topoisomerase II enzyme causing apoptosis
What is the mechanism of action of bleomycin?
Binds to DNA and intercalates
Can also chelate with Fe2+ to form free radicals that attack phosphodiester bonds
What is the mechanism of action of 5-fluorouracil?
Analogue of uracil and competes for binding site of thymidylate synthase preventing incorporation of pyramidines into DNA
What is the mechanism of action of methotrexate?
Inhibits dihydrofolate reductase preventing purine production
What are the constituents of mitotic spindle?
Alpha and beta tubulin
What is the mechanism of action of taxoids (spindle poison)?
Bind to beta tubulin subunit stabilising microtubules and inhibiting disassembly, can’t pull chromosomes apart
What is the mechanism of action of vinca alkaloids (spindle poison)?
Bind to beta tubulin subunit preventing microfilament formation, so no spindle formation
How can cancer become resistant to chemotherapy?
Decreased entry or increased efflux of agent
Inactivation of agent in cell
Enhanced repair of DNA lesions produced by alkylation
Drug target expression upregulated
What factors are considered before giving chemotherapy?
Performance score - how they are functioning
Clinical stage
Prognostic factors and molecular markers
Side effects
What are some common routes of administration for chemotherapy?
IV - central catheter, Hickman line
S/c injection
Direct intralesional
What are some general side effects of chemotherapy?
Alopecia Mucositis N&V Myelosuppression Diarrhoea
What pharmacological considerations need to be undertaken when starting a patient on chemotherapy?
Narrow therapeutic window
Significant side effects
Dose alterations - BMI, liver and renal function
Treatment phasing
What can cause abnormalities in absorption of chemotherapy?
N&V
Gut problems
What can cause abnormalities in distribution of chemotherapy?
Weight loss
Ascites
What can cause abnormalities in elimination of chemotherapy?
Liver and renal dysfunction
Other medications
What can cause abnormalities in the protein binding of chemotherapy?
Low albumin
Other drugs
Give examples of drug interactions involving chemotherapy drugs:
Vincristine and itraconazole - more neuropathy
Methotrexate and penicillin/NSAIDs
How should chemotherapy be monitored?
Response of cancer
Drug levels
Organ damage
What is salvage chemo?
Chemotherapy for relapsed disease
What specific renal side effects can chemotherapy have?
Acute renal failure due to hyperuricemia caused by rapid tumour lysis
What specific gastrointestinal side effects can chemotherapy have?
GI perforation at site of tumour
Mucositis
What specific haematological side effects can chemotherapy have?
Disseminated intravascular coagulopathy
Haematological toxicity - neutrophils, RBC, platelets
What specific hair and skin side effects can chemotherapy have?
Alopecia
Skin toxicity - Beau’s lines on nails, bleomycin
What specific cardiac side effects can chemotherapy have?
Cardiomyopathy
Arrhythmias
What specific respiratory side effects can chemotherapy have?
Pulmonary fibrosis - bleomycin
