Chemotherapy Flashcards
Short term complications chemo
Hair loss
Change taste
Loss appetite
Nausea
Fatigue
anaemia, TP, neutropenai
Tumour lysis syydndrome
What can prevent tumour lysis syndroe [re chemo
Rasburicase
Long term comps chemmo
Peripheral neuropathy
Cardiomyopathy - anthracycline
Hypogammaglobulinaemia - rituximab
Renal damage
Reduced fertility
Risk of secondary malignancy
Low grade lymphomas 30%
Indolent clinical behaciour
Non specific symptoms- disseminated
Littel scope for cure
Tend transform to high grade lymphomas
Intermediate and high grade lymphomas features
More aggressive but more responsive to chemo
Recurrence more common in first two ears
Relaps or resistance to chemo - poor prognosis <5-10%
Prognosis NHL general
2/3 survieve >10 years
IPI score for diffuse large B cell lymphoma
Age >60
Poor perfomance status - ECOG
Elevated LDH
>1 exrranodal site
Stage III or IV
FLIPI adds
<12 Hb
>4 nodal sites involvement
Sezary syndrome survival
<5 years
Different chemotherapy options
Single agent
COmbination
Monoclonal antibodies
Targeted treatments
Steroids
What aim of treatment w chemo
Curative
Disease control - keep at bay
Palliative - symptom
How does chemoterhayp work
Target different stages of cell cycle to prevent normal replciation of cancer cells
Cancer cells divide more than normal cells hence why targeted by them
Nomral cells affected = side effects
MOA alkylating agents
Alkylating agents cause cross links within DNA double helix by adding alkyl groups to guanine bases - DNA damage, cytotoxic in entire cell cycle
Alkylating agents exmaples
Cyclophospamide
Bendamustine
Chlorambucil
Melphalan
Ifosfamide
MOA of antimetabolite chemoterhay
Interfere w DNA and RNA synthesis act as substitute for normal DNA bases - C, A, T, G
Target S phase of cell cycle - cytotoxic when DNA being synthesised
Examples of antimetabolites
Purine analogues -fludarabine, 6-mercaptopurine
Pyrimidine analogues - cytarabine, gemcitabine, azacitadine
Antifolate - methotrexate
Anit-tumour antibiotics MOA
1 Intercalate between base pairs
2 Inhibit topoisomerase II
2 Create oxygen free radicals
Examples of anthracyclines
Daunorubicin
Doxorubicin
Epirubicin
Idarubicin
Bleomycin
Mitotic inhibitor/plant alkaloid MOA
Inhibit microtubule polymerisation
Bind to tubulin protine and inhibit formation, cant form microtubules
Interfere w mitosis phase of cell cycle
Examples of mitotic inhibitors
Vincristine, vinblastine
Steroids as chemotherapy MOA
Not fully understood
Steroids used in chemo
Oral - prednisolone, dexamethasone
IV - dexamethasone, methylprednisolone
Generic chemo side effects
Myelosupression - cytopenias
Gut toxicity - sore mouth , change in tast, diarrhoea, neutropenic coliti/typhylitis
N+V
Hair loss
Effect on fertility
Liver toxicity
Teratogenecity
Fatigue
Anthracycline specific side effects
Cardiac toxicity
Life tiem dose - cant exceed over life time
Vinca alkaloids side effects
Peripheral neuropathy
Constipation
Bleomycin side effects
ILD/fibrosis
Avoid in elderly, prev smokers
Ifosfamide side effects
Encephalopathy - only as inpatient, usually reversible
Long term chemo side effects
Cardiotoxicity, ILD
fertility problems
Bone problemms- steroids
Secondary malignancies incl haematological cancers - MDS,AML - poorer prognosis
Skin cancers
MOA of monoclonal antibodies
Target specific cancer cell protein and inducing antibodu depeneent cellular cytotoxicity - ADCC and completment depenent
Monoclonal ABs exmaples
Rituximab - CD20 bind (B cells)
Obinutuzumba - 2nd gen CD20
Daratumumab - anti CD38
Side effects of MoABs
Infusion related reactions -> fever, hypotension, rash, anaphylaxis
Increased suscetibility to infections - targets helathy B cells
How are ibrutinib and acalabrutinib targeted therapies
B cell receptro, bruton tyrosine kinase inhibitor - BTKi
What can use ibrutinib and acalabrutinib in
CLL, mantle cell lymphoma
How do imatinib, dasatinib, nilonitib, ponatibin in
Tyrosine kinase inhibitors
What are imatinib, dasatinib, nilonitib, ponatibin used in
CML, Ph + ALL
MOA of venetoclax
Bcl2 inhibitor (antiapotpic protien inhibited)
What use venetoclax in
CLL, AML
MOA of midostaurin and what use in
FLT3i
AML
Proteasome inhibitors examples
Bortezomib - velcade, ixazomib, carfilozimib
Immunomodulatory agents
Linalidomide, thalidomide
What targeted therapies can be used in myeloma
Proteasome is eg bortezomib, ixazomib, carfilzomib
Immunomod- lenalidomide, thalidomide
DA regime
Daunorubicin + cytarabine
Induction for AML
FCR use and what are
CLL
Fludarabine, cyclophos
VTD + IRD chemo what is and use
Myeloma
Velcade
Thalidomide
Dexamethasone
IRD - Izazomib, Revlimid, dexamathasone
How do cancer cells most commonly avoid T cell detection
PD-1 upregulation
Antibodies still sick but ineffective at killing cell and T cell wont recognise
What are Pd-1 inhibitors effective in/used in
Good results in hodgkins lymphoma
Used eztensively in solid cancers
Side effects of PD1 inhibitors
Autoimune disorders due to lack of PD1 on normal cells
Can be life threatening, can affect any organ
New approach to targeted haematlogical malignancy therapies
Activate T cells to identify tumour cells and -> cell lysis
What are CAR-T cells
Transfuse own T cells ‘infected’ with vector containing T cell receptor that can recognise antigen that want to target
How long does T cell ‘reset’ in CAR-T process take
4-5 weeks to get 6 T cells
How do bispecific antibodies work?
Antibody links T cell via CD3 receptor with target of interest specific antibodies
Brings T cell into proximity w cancer cells
CAR-T cells when become effective after transfusion
Each CAR-T cell can -> death of >100,000 tumour cells
10 mil when infuse, in 7 days -> 100-200 million
Current CAR-T cells available in UK
Zuma 1 - 3 transufsions
Tisagenlecleucel
ALL relapse what targeted therapy improves prognosis
Tisagenlecleucel
V poor prognosis
50% in remission 12 months post therapy
75% survival 12 months later
What may develop in first 10-14 days after CAR-T cell therapy
Cytokine release syndrome
What is cytokine release syndrome
Systemic inflam response caused by cytokines released by CAR-T cells and other immune cells -> reversible organ dysfunction
Presentation of Cytokine release syndorme
Neurologic
Haem - anaemia, TP, neutropenia, lymphopenia, DIC, HLH, coagulopathy etc
Constituational - fevers, rigors, malaise, anorexia, myalgia
CVS - tachy, hypotension, arrhtyhmias, QT prologen, decreased LVDEF
Pulm - hypoxia, tachy RR
Renal - AKI, electrolyte tumour lysis syndrome
N/V, diarrhoea
Elevated CK
Why need to give CAR-T cells as inpatient
Risk of cytokrine release syndrome
Cons of CAR-T cells
V expensive - 300,000 [pounds per dose
3-5 weeks to manafacture
Can only give once
Still high mortality rates
Potnetial advantages of bispecific antibodies vs CAR-T cells
Chepaer
Antibody infusion - multiple repeats
Can be gicen immediately
Toxicity v prediatbale within few hours of transfusion
Only need to stay in hospital for a few days
Causes of macrocytic anaemia
MDS
B12/foalte deficiency
Haemolytic anaemia
What does a positive IgG coombs test suggest
Red cells are coated with IgG
What does IgG being a warm antibody mean
Cant fix to complement
Ass w AIHA
Why does a direct positive IgG coombs test suggest extavascular haemolysis
Suggests RBC coated in IgG - recognised by macrophages in reticuloendothelial system and -> haemolysis in spleen
What does a postive coombs test with complement mean
Due to cold IgM antibodies
Where does haemolysis take place if direct coombs test complemetn positive
Cold IgM - intravascuarly as able recognised by complement therefore takes place intravascuarly
What does raised reticulocytes and direct positive IgG coombs test suggest in CLL
Extravascular haemolysis is occuring in spleen
What haematological malginancy is characterised by progressive failure of the immune system and gradual resistance to chemotherapy interventions
CLL
How long after splenectomy need antibitoics for and which ones
Penicillin or erythromycni
Minmum of two years, pssibly life long
What vaccinations shld patietns receive pre splenectomy
H.influenzae B
MenC
Pnuemococcus
Back pain red flags
Weight loss
No improvement after 2 months
Progressive or nocturnal pain
Fever
Pain at rest
Night sweats
Morning stiffness
Neurological disturbance
Sphincter disturbance
History of malignancy
What diuretics should you start vs stop in hypercalcemia
Start loop diuretics (reduce Ca levels in plasma - NA/K/2Cl ATPase - increased Na excretion->increased K+ secretion -> increased Ca and Mg excretion charge balacne )
Stop thiazide like diuretics - absorb Calcium
Most effective bisphosphonate in hypercalcemia
Pamidronate
Needs hydration first esp in renal failure
How are bisphophonaes used in muliple myeloma
-Treat hypercalcemia in emergency
- “bone strengthener” with monthly infusions; they are adsorbed onto bone hydroxyapatite crystals, slowing their rate of growth and dissolution, so bone turnover is reduced.
