modes of treatment Flashcards
what are the priorities in dealing with cancer
The priorities in dealing with cancer are:-
Prevention, Early Detection, Total Eradication BUT in most cases these are as yet unrealized ideals.
what are the hierarchy of aims in cancer management
Hierarchy of aims in cancer management:-
Cure - eradication of tumour and metastasis.
Remission/mitigation - significant reduction in tumour load. Increased survival.
Symptomatic / palliation - treatment of secondary complications. Relief of symptoms.
Terminal care - improve quality of life. Optimize symptom control.
is it possible to cure cancer?
For most solid tumours local control is possible but not sufficient for cure because of the presence of systemic (microscopic) disease, while haematological cancers are usually disseminated from the outset.
The likelihood of cure of the systemic disease depends upon the type of cancer, its chemo-/hormonal sensitivity, and tumour bulk.
A few rare cancers are so chemosensitive in adults that even bulky metastases can be cured, e.g. leukaemia, lymphoma, but for most common solid tumours such as breast and colorectal there is no current cure of bulky metastases but micrometastatic disease treated by adjuvant therapy after surgery can be cured in 10-20% of patients.
what is palliation?
how long does palliation pro-long life for?
When cure is no longer possible, palliation, i.e. relief of tumour symptoms and prolongation of life, is possible in many cancers in proportion to their chemo- and radiosensitivity. There is on average a 2-18 months prolongation in median life expectancy with current treatments for solid tumours and up to 5-8 years for some leukaemias and lymphomas.
The development of more effective chemotherapeutic drugs and better supportive care such as antiemetics has done much to reduce the side-effects of chemotherapy and to improve the cost/benefit ratio for the patient receiving the palliative treatment.
- does not matter when giving opioids are given to patients in palliative care because it doesn’t matter if they get dependent as long as they are happy and feeling good.
what are the modes of therapy for cancer?
The method of treatment will largely be determined by a realistic assessment of the therapeutic goal. The usual modes used are:-
1. Surgery - excision of primary tumour.
2. Bone marrow transplantation - for some leukaemias.
3. Radiotherapy
4. Drugs - cytotoxic chemotherapy, hormone therapy, immunotherapy.
why is it hard to surgically remove cancer?
As malignant neoplasms invade the surrounding tissues it is hard to surgically remove all of the cancer, and adjuvant therapy is normally required (e.g. radiotherapy for local invasion and lymph node spread, drugs for more disseminated cancers).
what are the two factors which govern which treatment to use?
Two factors govern which treatment to use –
i) empirical clinical evidence; ii) practical considerations.
when should you use a surgery?
Well-defined solid tumour
Non-vital region (e.g. mastectomy)
Non-mutilating result
Resection/reconstruction possible (e.g. gut)
when should use a radiotherapy?
Diffuse but localized tumour (e.g. lymphoma)
Vital organ / region (e.g. head and neck, CNS)
Adjuvant therapy (e.g. post mastectomy)
Palliation
when should you use chemotherapy?
Adjuvant therapy following surgery or radiotherapy
Neo-adjuvant therapy prior to surgery or radiotherapy
Widely disseminated / metastasized
Diffuse tumour (e.g. leukaemia)
Palliation
Some primary tumours (e.g. Hodgkin’s lymphoma)
how does chemotherapy work to treat cancer?
Chemotherapeutic agents exert their effect by killing cells that are rapidly dividing. The agents are therefore NOT tumour specific but also kill normal rapidly dividing cells such as hair follicle cells and gastrointestinal mucosa.
hence why there is symptoms such as loosing hair (when effecting hair follicle) and GI effects and mouth ulcers (when effecting GI mucosa)
how does radiotherapy work to treat cancer?
Radiotherapy is the application of ionizing radiation to treat disease - electromagnetic radiation and elementary particles deposit energy in materials through the processes of excitation and ionization events.
what is the rationale of chemotherapy
Chemotherapy is the systemic treatment most commonly used to treat advanced cancer. In a limited number of cases it is the sole treatment for cancer (e.g. chemosensitive cancers such as leukaemia).
For the majority of the solid tumours chemotherapy is used to reduce the volume of disease and palliative symptoms caused by cancer.
A further indication for chemotherapy is to use it as an adjuvant after the primary tumour has been controlled by either surgery or radiotherapy - this is to eradicate subclinical micrometastatic disease and reduce the risk of recurrence. ( to mop up anything which is left over/missed ) - after surgery/radiotherapy
Neoadjuvant chemotherapy is also used increasingly to debulk or downstage primary tumours prior to the definitive treatment, eg surgery or radiotherapy. - (Make the tumour smaller so when doing the surgery it’ll be smaller to take out when doing the surgery.) - before surgery/radiotherapy
Chemotherapy is usually used systemically either intravenously or orally.
To understand the rationale of cytotoxic chemotherapy it is important to recognise the features of tumour growth - factors responsible for determining the growth of a tumour include the cell cycle time, growth fraction, number of cells.
By the time tumours are clinically apparent (around 109 cells or more) most tumours are in the relatively slow phase of growth - this is the time that chemotherapeutic agents are least likely to prove effective. ( the centre of the tumor is further away and they already had their rapid growth time )
Chemotherapeutic agents are used in combination rather than as sequential single therapies. The combination of drugs chosen should have a minimal overlap in toxicity.
The treatment should be delivered on an intermittent basis with the SHORTEST possible time between treatments that allows recovery of the most sensitive normal tissue (e.g. bone marrow or gut). - 3 week cycle
Wherever possible it is preferable to use drugs with known synergistic killing effects, for example the combination of oxaliplatin and 5-fluorouracil. ( they work better together than by themselves)
Another possibility is to use a combination of drugs that can kill cancer cells at different stages of the cell cycle.
Some regimens use alternating cycles of different drug combinations - giving the less effective drug first.
current drugs that target the cell cycle
week 26, mode of treatment , slide 12 and 13
what are the cytotoxic side effects of chemotherapy
Myelosuppression - most drugs cause rapid falls in peripheral blood count. Leucopenia results in immunosuppression and frequent infections. Thrombocytopenia (reduced platelet count) impairs coagulation leading to bruising and bleeds.
Gastrointestinal tract and bladder - Erosion and ulceration is very common especially in mucous membranes, causing e.g. mouth ulcers or diarrhoea.
Fertility - Spermatogenesis is inhibited and sometimes there may be permanent male infertility, e.g. from alkylating agents. Female infertility is less common.
Teratogenic action - cytotoxics are particularly hazardous during the first trimester of pregnancy, I.e. during organogenesis and the risk is greatest for methotrexate and the alkylating agents.
Skin and hair - hair loss is common and although reversible it is very distressing.
what are the mutagenesis side effect of chemotherapy
Most cytotoxics act by damaging DNA, and the effect of the resultant change in the genome depends on whether somatic or germ cells are affected.
Genetic damage - heritable defects may be caused if the DNA of spermatazoa or ova is damaged, although most mutations are lethal for the cell. These risks are yet to be fully assessed but are avoided by contraception during treatment.
Carcinogenesis - cytotoxic drugs are able to both cause and cure cancer. The same is true for radiotherapy. Hence more selective methods for treating cancer are required.
what are the other side effects of chemotherapy?
Nausea and vomiting - the effects can last for several days after treatment and prevents some patients from continuing with therapy. The symptoms result from direct stimulation of the chemoreceptor trigger zone. Anti-emetics are therefore used alongside traditional chemotherapy regimens.
Other effects - each class of drugs has its own characteristic adverse effects on major organs. Some important examples are provided :-
how can you minimise side effects?
Many strategies have been devised to reduce the damage done to normal tissues by cytotoxic drugs. The aims are to either reduce discomfort, morbidity and mortality or to increase the tolerable dose threshold and thus the dose that can be used.
Close monitoring is extremely important particularly full blood counts.
Prevention is used wherever possible, e.g. by allowing adequate time for marrow recovery between treatments, or by administering stem cell growth factors with chemotherapy to selectively enhance marrow proliferation.
Forced diuresis is now routinely given with nephrotoxic and bladder-toxic drugs to reduce contact time and urine concentration. This involves modest over-hydration before therapy followed by a diuretic to maintain a high urine output for at least 24h following therapy (e.g. mannitol).
how to control myelosupression (side effect)
Transfusions - Blood platelets, granulocytes, autologous blood/marrow
Growth factors - Filgrastim
Timing of doses, careful monitoring, isolation in sterile environment
how can you minimize nausea and vomiting?
Anti-emetics : dopamine antagonists,
5HT3 antagonists,
benzodiazepines,
corticosteroids,
cannabinoids
e.g
Prochlorperazine, metoclopramide
Ondansetron
Lorazepam
Dexamethasone
Nabilone
what do you minimize mouth ulcers / mucositis
oral hygiene
- mouth washes
what do you minimize sub fertility
sperm banking
ivf
e.g - filgratism
what do you minimize cardiomyopathy?
ECG monitoring; cardiac glycosides
what do you minimize hepatotoxicity?
LFT - post and pre
what do you minimize anti-folate overdose
for methotrexate
- folinic acid rescue
what do you minimize Nephrotoxicity / Haemorrhagic cystitis
Hydration and forced diuresis (for ifosfamide and cyclophosphamide)
-mesna
what do you minimize alopecia?
Scalp tourniquet or chilling, wigs
how can you measure response to treatment?
A measurable response to treatment can serve as a useful early surrogate marker when assessing whether to continue a given treatment for an individual patient.
Definitions of responses:-
Complete response: complete disappearance of all detectable disease.
Partial response: More than 50% reduction in the product of the bidimensional diameters of the tumour
Stable disease: No change, or <50% reduction and <25% increase
Progressive disease: Increase in size of tumour by at least 25% at any site
