Chemotherapy Flashcards
How long does the cell cycle last?
Varies from 9 to 43 hours
Why are non-growing micro-metastases often a problem in chemotherapy?
It cannot target cells in G0
However can get drugs which push them out of G0
Name some tumours that are highly sensitive to chemotherapy
Lymphoma
Germ cell tumours
Neuroblastoma
Wilm’s tumour
Name some cancers which have low sensitivity to chemotherapy
Prostate
Renal cell
Brain tumours
Endometrial cancer
What are the different ways tumours can spread?
Local
Lymphatic
Blood
Implantation
What are the different options for using chemotherapy?
Primary treatment - radical, first line treatment
Adjuvant - post-operative, when at high risk of metastases after removal of the primary tumour
Neoadjuvant - primary treatment in a localised tumour, assess biological responsiveness and before surgery to reduce tumour size
Palliative - in advanced disease
Salvage - in relapsed disease
What is the Philadelphia chromosome?
An oncogene where there has been a translocation of 9 to 22
Seen in chronic myeloid leukaemia
Which chemotherapy targets the Philadelphia chromosome?
Imatinib
What is the mechanism of action of imatinib?
Bcr-Abl tyrosine kinase inhibitor
What is tyrosine kinase?
An enzyme that can phosphorylate proteins from ATP
When switched on permanently, can cause unregulated cell growth
What is the mechanism of action of chemo drugs ending in ‘nib’?
Inhibit tyrosine kinase
Why is chemo normally administered in pulses?
Depletes bone marrow as well as tumour cell population
Allows bone marrow cells to recover and they recover to higher level than cancer cells can in that time
When would chemotherapy be given continuously?
When they need a bone marrow transplant
Mechanism of action of antimetabolites?
Stop DNA synthesis
Mechanism of action of alkylating agents?
Bind to DNA and fix it so that it cannot be unwound and replicated
Mechanism of action of intercalating agents?
Affect DNA transcription and duplication
Mechanism of action of spindle poisons?
Stop mitosis by preventing polymerisation and depolymerisation of spindle fibres in anaphase
Mechanism of action of platinum?
Forms platinated inter- and intra-strand adducts
Each adduct has a large side-group, stopping replication and inhibiting DNA synthesis and apoptosis
Mechanism of action of topoisomerase-1 inhibitors?
Inhibit re-ligation of a DNA strand when it has been cleaved due to supercoiling
Therefore have single and double stranded breaks, causing apoptosis
Mechanism of action of methotrexate as a chemo drug?
Inhibits dihydrofolate reductase, stopping production of purines
Mechanism of action of 5-fluorouracil?
Stops the folate cycle, inhibiting production of pyrimidine bases
Mechanism of action of vinca alkaloids and taxoids?
Vinca alkaloids - inhibit polymerisation of spindle fibres
Taxoids - inhibit depolymerisation of spindle fibres
What is response to chemotherapy based on?
Performance score of an individual patient
Clinical stage
Prognostic factors/score
Side effects vs anticipated/best outcome
How is the performance score calculated?
0 = full health 1 = jaded - can do activities but struggle at work 2 = cannot work, spends 50% of day resting 4 = bed-bound 5 = dead
Routes of administration of chemotherapy drugs?
IV
- bolus
- infusional bag
- continuous pump infusion
PO SC Into a body cavity Intralesional Intrathecally Topically IM
Types of IV pumps for chemo?
PICC line - a peripherally inserted catheter. Patient can go home with it. Well tolerated.
Hickman line
What are the mechanisms of resistance to alkylating agents?
P-glycoproteins allow the drug to enter the cell, but can be modified to pump it straight back out again before causing damage
Drug inactivated/neutralised by proteins in the cytoplasm eg glutathione. Bind to it and drug is no longer harmful so cannot get to genetic material in nucleus
Enhanced repair mechanisms of DNA once damage has been done
How can renal failure occur with chemo?
Often multi-factorial
Hyperuricaemia caused by rapid tumour lysis leads to precipitation of urate crystals in renal tubules
What are the different patterns of emesis with chemo?
Acute phase: 4-12 hours
Delayed onset: 2-5 days
Chronic phase: persist for up to 14 days
Which chemo causes minimal alopecia?
Platinum
What skin toxicity is there in chemo?
Locally
- irritation and thrombophlebitis of veins
- local extravasation, goes into surrounding tissue instead of vein, leading to necrosis. Higher risk with poorer veins
General
- bleomycin can cause hyperkeratosis, hyper-pigmentation, ulcerated pressure sores
- Beau’s lines on nails
How does mucositis present with chemo?
(GI epithelial damage)
Sore mouth and throat with many ulcers - commonly worse in oropharynx
Diarrhoea
GI bleed
What problems with the heart can chemo cause?
Cardiac myopathy (doxorubicin and cyclophosphamide)
Arrhythmias (cyclophosphamide and etoposide)
What lung toxicity can chemo cause?
Pulmonary fibrosis
-do not give oxygen, makes it worse
Give a summary of ADRs of chemo
Acute renal failure GI perforation at site of tumour Disseminated intravascular coagulopathy Vomiting Alopecia Skin toxicity - thrombophlebitis, extravasation, hyper pigmentation Mucositis Cardio-toxicity - cardiac myopathy and arrhythmias Haematological - neutrophils and platelets Cystitis Myalgia Neuropathy Sterility
How can absorption of chemo be affected?
Nausea and vomiting
Compliance
How can abnormalities in distribution of chemo occur?
Can sit in ascitites
Weight loss
Reduced body fat
How can abnormalities in elimination of chemo occur?
Liver and renal dysfunction
Other medications
How can abnormalities in protein binding occur in chemo?
Low albumin
Other drugs
Important DDIs of chemo?
Vincristine and itraconazole (anti fungal) - increased neuropathy
Capecirabine (oral 5-FU) and warfarin
Methotrexate and penicillin or NSAIDs
Cepcitabine and St. John’s Wort or grapefruit juice
What factors affect the dose of chemo given?
The patient’s BMI and/or surface area
Drug handling ability of the patient eg liver function, renal function
General well-being - performance status and co-morbidities
How is the response of cancer to chemo monitored?
Radiological imaging
Tumour marker blood tests
Bone marrow cytogenics
What other monitoring is done with chemo?
Drug levels eg methotrexate drug assays to ensure clearance from the blood
Organ damage eg creatinine clearance of echocardiogram
What is the ultimate measure of trial outcomes?
Overall survival
