cancer therapies Flashcards
what’s the rationale behind chemotherapy?
targets key players in cell cycle to prevent progression of the cell cycle and thus induce apoptosis therefore cytotoxic
therefore mainly affects rapidly dividing cells.
what are the different ways in which chemotherapy is used?
neoadjuvant - shrink tumour before surgery.
adjuvant - after surgery to reduce chance of prolapse by reducing any micromets
primary therapy - haematological malignancies
palliative - symptom control, prolong life and improve quality
maintainance therapy - maintain growth of cancer to a minimum can last from weeks to years depending on cancer and how well side effects are tolerated
what are the pros and cons of neoadjuvant chemotherapy?
improves surgery outcome
can see the impact of chemo - can visualise the shrinkage
however delays surgical time and thus gives opportunity for progression
what are the pros and cons of adjuvant chemotherapy?
can reduce chance of micrometastasis
however cant monitor whether it is having an effect just hope it doesn’t reoccur
list the different classes of chemotherapy agents. give an example of each.
antimetabolites - methotrexate, 5 flurouracil
alkylating agents - cyclophosphamide
platinums - cisplatin
vinca alkaloids and taxanes - vincistrine
DNA interfering agents - bleomycin
DNA topoisomerase inhibitors - doxorubicin
what do alkylating agents do? (chemo)
bind alkyl groups on DNA and cross link DNA strands
what do platinums do? (chemo)
work in a very similar way to alkylating agents and cross link DNA but in a different way. they also intercalate DNA
what do antimetabolities (chemotherapy) do ? use 2 examples
mimic normal substrates to block the production of metabolites needed for replication.
e. g. methotrexate block DHFR and thus reduces nucleotide production
e. g. 5 flurouracil - inhibits thymidylate synthesis and thus thymine cannot be produced
what do vinca alkaloids do?
mitotic inhibitors - inhibit formation of microtubules
what does bleomycin do?
DNA interfering agent - inserts itself into DNA to prevent replication
what does doxorubicin do?
topoisomerase inhibitor.
topoisomerase normally helps stabilise DNA during replication by preventing supercoiling.
therefore doxorubicin causes supercoiling and cessation of DNA replication
chemotherapy agents have a narrow therapeutic index what does this mean when we calculate doses for patients?
need to be careful and calculate dose for each individual patient depending on
- BMI and body surface
- their ability to metabolise the drug - kidney and renal function
- general well being (performance status)
to avoid toxicity
how are chemotherapy agents delivered to the patient?
IV, oral or subcutaneously
what is the problem with delivery some chemotherapies peripherally?
chemotherapies are quite toxic drugs and thus can damage peripheral veins
can cause extravasation - local tissue necrosis of peripheral vein
what is meant by a chemo cycle? how long is a cycle?
chemotherapies are usually prescribed in cycles to allow bone marrow recovery between each cycle
length of cycle and no. of cycles depends on drugs
why do cancer cells develop resistance quickly and how can we aim to combat this?
rapidly dividing and genetically unstable and thus have a high mutation rate.
so can quickly develop mutations giving them resistance against chemotherapy agents
when using multidrug regime of chemo to combat resistance what must we ensure about the different drugs?
different targets
different toxicity
different mechanisms of resistance
what are the different resistance mechanisms cancer cells develop?
efflux pumps - ejection of chemo agent decrease uptake of drug increase drug metabolism alter drug target increase expression or affinity of target enzyme impair apoptotic pathways
why do chemotherapies have many side effects?
not selective to tumour cells alone.
target any rapidly dividing cell and thus other tissue types in the body are affected - gut, bone marrow, hair follicles etc
list the common side effects of chemotherapy
hair - alopecia - reduces self esteem
brain - chemobrain (cant function the same), peripheral neuropathy, fatigue, psychological distress
lungs - pneumonitis leads to SoB and restrictive lung pattern and ILD e.g. bleomycin. also can get P.Es
heart - cardiomyopathy
stomach/ GIT - N+V, diarrhoea/ constipation and mucositis
liver - deranged LFTs
kidney - AKI, electrolyte disturbance
bladder - haemorrhagic cystisis
repro - impaired fertility, premature menopause and reduced labido
skin - rash, nail loss, palmar plantar erythema (dry hands and feet)
blood - myelosuppression
how can we prevent anticipatory nausea and vomiting?
prevent N+V on first chemo dose
what is the problem with mucositis ?
painful oesophagus and mouth
can prevent eating
predisposed to thrush
what are beau’s lines?
with chemo you get nail loss and thus with each cycle of chemo a line is shown on your nails. count the lines = no. of cycles
chemotherapy can cause myelosuppression what can this lead to?
anaemia - fatigue, SoB
thrombocytopenia - bleeding
neutropenia - infection and sepsis
how is nausea and vomiting from chemo managed?
anti emetics
ondansetron - given on day of chemo and 3 days later - prevent N+V so that anticipatory N+V doesn’t develop
metoclopramide - when needed
dexamethasone and PPI - not in diabetes
others - cyclizine and aprepitant
how is alopecia from chemo managed?
cold pack on head - vasoconstriction to reduce chemo agents getting to the scalp - reduces hair loss
everyone gets a wig referral
how is infection risk from chemo reduced?
prophylactic:
- antifungals - intraconazole
- co-trimoxazole - pneumocystis jivoreci
- Abx
- antivirals - aciclovir
mouth wash with chlorhexidine is recommended after every meal - mouth is main source of infection
regular blood tests to check for neutropenia
how is mucositis from chemo treated?
mouth care
treat infection
can give prophylactic fluconazole for thrush
chemotherapies are teratogens - how is this effect avoided?
advice to avoid pregnancy in both men and women
should use contraception but avoid COCP - thrombosis risk
chemotherapy reduces fertility, how can we help patients with this problem?
council patients on this risk
offer egg freezing and sperm storage
how can we help someone on chemo with a very low Hb count? when is this not advised?
can consider transfusion
however if WCC > 100 x 10^9 then contraindicated due to hyperviscosity
where do PICC and Hickmans lines insert?
PICC - peripherally inserted central catheter - use peripheral vein and thread it through until it reaches a central vein
Hickmans - into SVC via chest wall.
what is immunotherapy?
uses the bodys own immune system and its components to target and destroy cancer cells
involves monoclonal Ab, checkpoint inhibitors, cytokines, interferons and interleukins
how are monoclonal Abs made?
inject antigen into mice and allow them to develop B cells against this antigen
hybridise this B cell with a myeloma cell such that the B cell replicates indefinitely to supply these specific Ab indefinitely
give 4 examples of monoclonal antibody use in cancer.
Herceptin - HER2 receptor blocker in HER positive breast cancer
Avastin - blocks VEGF to prevent angiogenesis in breast and gastric cancers
EGFR blockers - (these can be monoclonal ab but can also get small molecule inhibitors against them) - mainly used in CRC. (EGFR is a tyrosine kinase implicated in proliferation, invasion and reduced apoptosis
rituximab - against CD20 - good for B cell lymphoma
explain how checkpoint inhibitors work
our body cells express PDL1 ligand which can bind T cell and APC PD1 receptors. This allows immune cells to recognise self from non-self. tumour cells have found a way to express PDL1 such that the APC/ Tcells do not destroy them.
checkpoint inhibitors aim to block the PDL1/ PD1 interaction and thus allow tumour cells to be recognised by immune system and destroyed.
these inhibitors are monoclonal Ab
what is imipilumumab
monoclonal Ab used as a checkpoint inhibitor in myeloma
explain the side effect effects found with immunotherapy?
immunotherapy is effectively activating the immune system and thus can result in:
autoimmunity - thyroid, addisons, hypopituitarism, neurological autoimmune conditions, myasthenia, arthritis, vasculitis, guillian barrie, polymyalgia rheumatica etc
inflammation - hepatitis , mucositis (diarrhoea, N+V, adbo pain) , immune related dermatitis, pruritic, steven Johnson, pneumonisitis
side effects can last for months after dose
how is autoimmunity as a result of immunotherapy treated?
steroid and immunosuppression
what are targeted therapies?
small molecule inhibitors that target specific drivers of the cancer e.g. tyrosine kinase inhibitors
these molecules end in ib
give an example of a targeted therapy
Imantinib - tyrosine kinase inhibitor in CML (BCR ABL inhibitor)
what are the side effects of targeted therapy?
HTN, proteinuria, GI perforation and poor wound healing are the main 4
others - diarrhoea, N+V, abnormal LFTs hair growth abnormalities , nail changes, pruritic, cardiac ischaemia, VTEs flu like symptoms and allergies myelosuppression, fatigue
what are the 2 ways radiotherapy works to kill tumour cells?
directly damages DNA with ionising radiation
produces free radicals which then damage DNA - need to ensure Hb levels are high enough in order for there to be O2 to produce free radicals
damaged DNA signals the cell to apoptose if it cannot be repaired (often tumour cells are genetically unstable)
how are normal cells protected from radiotherapy?
firstly radiotherapy is directly to tumour and minimises the effect it has on surrounding normal tissue. - done by careful calculation of tumour dimension
secondly normal cells have intact repair mechanisms and thus are more likely to repair before undergoing apoptosis
what are the different types of radiation therapy?
external beam (most common) - delivers radiation from an external accelerator
brachytherapy - radiation source is placed close or within tumour allowing high dose locally e.g. prostate or cervical
systemic treatments - radioactive substances injected/ swallowed and targeted to the tumour site.
what is the difference between radical and palliative radiotherapy?
radical:
- intent to cure
- low daily dose, high total dose
- 4-7 weeks of treatment
- small fields of radiation
palliative:
- reduce symptoms e.g. brain mets, bone pain, haemoptysis and dysphagia
- 1 to 10 treatments
- larger field of radiation
- high daily dose - low total dose
what are the early side effects of radiotherapy?
symptoms depends on site
tiredness - weeks to months
skin reactions - can vary from erythema to ulcers. use moisturiser to prevent
mucositis - avoid smoking, alcohol and spicy foods. aseptic mouthwash. treat oral thrush
N&V - caused by stomach, liver and brain radiotherapy
dysphagia and sore throat
diarrhoea - abdo and pelvic treatment. maintain hydration and give loperamide
cystitis - after pelvic treatments
bone marrow suppression
lymphaedema
hair loss
what are the late side effects of radiotherapy involving CNS and lung?
years to months later
CNS
- drowsiness after brain radiation (steroids to treat)
- spinal cord myelopathy - progressive weakness. MRI to rule out compression
- brachial plexopathy - after axillary radiation
- reduced IQ in those receiving brain radiotherapy before age 6
lung - pneumonitis and fibrosis (dry cough and dyspnoea). treat with steroids
what are radiosensitisers?
agents given that make tumour more sensitive to radiotherapy
conventional chemotherapy can be used in combo with radiotherapy to make radiotherapy more effective because chemo dysregulates the S phase which will reduce repair caused by radiation
e.g. cisplatin cross links DNA exacerbating the effect of radiotherapy on DNA damage
what is radioimmunotherapy?
radiolabelled monoclonal Ab
delivers cytotoxic radiation to target cancer cells
what is the role of surgery in cancer?
surgical biopsy for histological diagnosis - gold standard for cancer diagnosis
surgery with curative intent is main treatment for solid cancers
palliative care:
- stents to relieve obstruction
- insertion of Pegs
- abdominal shunts to relieve ascites
- debulking of large tumours that have obstructing affect e.g. SVC compression, dysphagia
what are the different methods of biopsing cancer?
FNA
-can be under image guided. try avoid tumour seeding
needle core biopsy
- involved a cutting needle. try avoid tumour seeding
open surgical biopsy:
- usually whole excision rather than incision
what are the side effects of surgery for cancer?
surgical complications - DVT, chest infection, surgical wound infection, bleed
anaesthetic risk
later - adhesions, strictures
nerve damage
specific problems e.g. short bowel syndrome
how is metastatic disease normally treated?
initial treatment leads to a new stable state
stable state which is maintained by long term cytostatic treatment e.g. immunotherapy
eventually relapse
is all metastatic disease incurable?
no, seminoma is metastatic but still can be cured quite well. however in generally usually poor prognosis
how are neuroendocrine tumours treated?
somatostatin analogues
need to check if they respond to somatostatin first - octreotide scan will test for this - shows up if somatostatin receptors are present or not.
what is the role of steroids in oncology?
reduce tumour size/ inflammation for cord compression
reduce N+V
increase appetite and weight gain
increase energy levels
reduce liver capsular pain when there are liver mets by reducing inflammation
can radiotherapy be given twice?
not to the same place, too damaging
what are the late side effects of radiotherapy involving skin, bone, GI, heart?
skin - pigmentation, ulceration, telangiectasia, necrosis
bone - necrosis, fracture, impaired growth (children)
GI - xerostomia, benign strictures, adhesions, fistulas
heart - cardiomyopathy, pericardiafibrosis
what are the late side effects of radiotherapy involving gonads, eyes, urinary and thyroid?
gonads - infertility, impotence, early menopause
eyes - cataracts, reduced vision
urinary - increased frequency due to small fibrosed bladder
hypothyroid
