Chemo Flashcards
2 main risk factors for chemo related cardio tox?
Age
Cumulative anthracycline dose
Cockroft gault equation
= (140-age)x weight) / 72x creat
Then multiply by 0.85 if female
Afatinib
Anti EGFR TKI NSCLC metastatic (NICE approved)
Aflibercept
Fake receptor with a antibody backbone
Binds VEGFA VEGFB and placental GF with a higher affinity than their endogenous receptors
Improves PFS and OS in mCRC when combine with folfiri 2nd line in patients who had folfox +- Bev in first line
Alemtuzumab
Aka CAMPATH
Anti CD52 monoclonal antibody
CD52 is on both T cells and B cells
Used for CLL in second line
Bevacizumab how does it work?
Binds VEGF, mostly VEGFA stopping it activating the VEGF receptor
Bortezemib (Velcade)
Small molecular proteasome inhibitor
Cell can’t clear toxic misfolded proteins
Suppresses NFkappaB (which normally promotes cell proliferation and survival)
Bosutinib
BCR-ABL inhibitor
CML in 3rd line
Is available on the CDF!
Treatment of CLL lines 1,2 and 3
First Imatinib
2nd nilotinib or dasatinib
3rd Bosutinib
Cabozantinib
MET and VEGFR2 inhibitor
MET unregulated in cells resistant to Antiangiogenics
Advanced medullary thyroid cancer and RCC
What kind of antibody is cetuximab?
Chimeric monoclonal antibody
Crizotinib
ALK and MET inhibitor
4-5% of NSCLC and majority of anaplastic large cell lymphomas
Dabrafenib
BRAF inhibitor inhibits V600E BRAF
BRAF Is mutated in 50% of melanomas
Erlotinib
Anti EGFR TKI
NSCLC
Everolimus
MTOR inhibitor
What is MTOR? What does MTOR inhibition do?
Intracellular serine-threonine kinase
Is downstream of the PI3K/AKT pathways which is often overactive in malignancy
Inhibiting MTOR lowers VEGF levels
Vismodeginib
Hedgehog pathway inhibitor - hedgehog pathway is overactive in BCC
Drug associated with Lhermitte’s syndrome? Tingling when bend neck
Cisplatin
Which protein do Taxanes stimulate the expression of in order to trigger apoptosis?
Bim
Bcl related pathway
How does Imatinib work?
Blocks the activity of the Bcr/abl fusion gene, restoring Bim and Bad apoptotic function
What are type 1 and 2 programmed cell death?
Type 1 apoptosis
Type 2 autophagy - MTOR PI3K/AKT regulated
What is the first stage in angiogenesis?
Localised degradation of the basement membrane of the parent venue
Does tamoxifen increase risk of endometrial cancer?
Yes
Does raloxefine increase risk of endometrial cancer?
No- it’s still an agonist in the uterus but is not as active as tamoxifen in the uterus
What vascular complication is raloxefine associated with?
Stroke
It does not increase risk of coronary artery disease
In which group does bisphosphonate use reduce the recurrence rate of breast cancer?
Post menopausal women
Monoclonal ab which causes both a early and delayed neutropenia
Rituximab
Which lymphoma has germinal B and non germinal B subtypes with an impact on prognosis? Which is worse?
DLBCL can be divided into germinal B and non germinal B
Either gene profiling or Hans criteria
Non germinal centre has a worse prognosis only 30% 5 years survival
What are two advantages denosumab has over bisphosphonates?
Less nephrotoxic
Longer time to first skeletal event
% risk cardiomyopathy with doxorubicin?
3%
Mechanism of action of Erubulin?
Microtubule inhibitor
How many more times potent than hydrocortisone is:
Pred
Dex
4: 1 pred
25: 1 dex
Ibrutinib use
Mantle cell lymphoma
Afanatinib use
NSCLC
Trametinib melanoma mechanism
MEK inhibitor melanoma
Target of Imatinib
BCR/ABL
When does the interstitial lung disease of TKIs usually present?
Within 1 month of starting
Should Erlotinib be taken on full or empty stomach?
Empty stomach- if take with food absorb more and get more toxicity
Which drug causes visual disturbances where when patient sees you walk they see a trail behind you?
Crizotinib (inhibits ALK and c met)
What does carbamazepine do to pazopanib levels?
Carbamazepine induces CYP450 so will lower levels of pazopanib
What does phenytoin do to pazopanib levels?
It induces CYP450 so levels of pazopanib will fall
What does ketoconazole do to pazopanib levels?
It inhibits CYP450 so get higher levels of pazopanib don’t clear it as much
What is the T790M mutation associated with?
Acquired resistance to anti EGFR TKIs
What is the T315I mutation associated with
Acquired resistance to BCR-ABL TKIs
Which chemo drug is affected by levels of TPMT deficiency?
6 mercaptopurine
Deficiency of TPMT get higher haematological toxicity which can be fatal
Which drug metabolism is UGT1A1 associated with?
Irinotecan
Polymorphisms leading to reduced level of this enzyme lead to higher rates of Irinotecan toxicity
When do you need to give mesna? (With which drugs?)
Everyone having ifosfamide
Only with high dose cyclophosphamide
How does mesna prevent haemorrhagic cystitis?
Provides a S-H group which binds to toxic metabolites of ifosfamide and cyclophosphamide
How do you know how much mesna to give?
60% of the dose of the alkylating agent in divided doses
every 4 hours
What drug do you have to give b12 and folate to the patient before you start it and why? When do you give it?
Pemetrexed
Start it 1 week before chemo and continue for 21 days after finish
Minimises toxicities
How can acute doxorubicin toxicity be minimised? Is it reversible or irreversible?
It is reversible
Can minimise by slowing down infusion rates
What is the P-glycoprotein pump on cells?
It is a multi drug resistance efflux pump
Which route of administration of Bortezemib minimises peripheral neuropathy?
SC Administration (it can be given IV or SC)
Mechanism of action of Abiraterone?
Irreversible inhibitor of CYP17
What is ofatumumab used for?
Refractory CLL
It’s anti CD20 like rituximab
