Cancer Therapeutics: Modes of treatment Flashcards
What are the three management aims and objectives for cancer treatment
Prevention
Early Detection
Total Eradication
PET
Describe each hierarchy cancer management aims
- Cure: eradication of tumour and metastasis
- Remission and mitigation: significant reduction in tumour load
- Symptomatic/Palliation:
Treatment of secondary complications, relief of these symptoms - Terminal Care:
Improvement of quality of life to optimise symptom control
What is possible for solid tumours in terms of a cure and why is this the case?
- Local control but not sufficient for cure
2. Due to presence of systemic (microscopic) disease
Even if bulky metastases are present, which rare cancers are chemosensitive
Leukaemia
Lymphoma
What is palliation
The relief of tumour symptoms and prolongation of life when a cure is no longer possible
What is the average life expectancy for someone with a solid tumour or leukaemia and lymphomas
Solid: 2-18 months
Leukaemia and lymphomas: 5-8 years
What are the four different modes of therapy
Surgery: excision of primary tumour
Bone marrow transplant: for some leukaemia’s
Radiotherapy
Drugs: cytotoxic chemotherapy, hormone therapy, immunotherapy
Give an example of adjuvant therapy
Radiotherapy for local invasion and lymph nodes spread: drugs for more disseminated cancers
Describe what to use surgery on (tumour type etc)
Well defined tumour
Non vital region (mastectomy- breast removal)
Non-mutilating result
Resection and reconstruction possible
Describe what to use radiotherapy on (tumour type etc)
Diffuse but localised tumour (lymphoma)
Vital Organ/region (head, neck, CNS)
Adjuvant Therapy: post mastectomy
Palliation
Describe what to use chemotherapy on (tumour type etc)
Diffuse tumour (leukaemia)
Palliation
Primary tumour (hodgkin’s lymphoma)
Adjuvant therapy
When does neo-adjuvant therapy take place
Prior to surgery or radiotherapy
How do chemotherapy agents exert their effect
Killing cells which are rapidly dividing
Agents are not tumour specific but also kill normal rapid dividing cells like hair follicles and GI mucosa
How do radiotherapy agents exert their effect
Application of ionising radiation to treat disease
Electromagnetic radiation and elementary particles deposit particles through excitation and ionisation
Common forms: ionising radiation include photon beams (X rays and gamma rays) and electrons (Beta particles)
Causes double strands of DNA to break which is completely irrepairable
What are the palliative benefits of radiotherapy
- Pain relief (bone metastases)
- Reduction of headache and vomiting of raised intracranial pressure from CNS metastases
- Relief of obstruction of bronchus, oesophagus, ureter and lymphatics
- Preservation of skeletal integrity form metastases in weight bearing bones
- Reversal of neurological impairment from spinal cord or optic nerve compression by metastases- can cause neurological issues
What are the acute side effects of radiotherapy
Anorexia, Nausea, malaise
Mucositis e.g. diarrhoea, oesophagitis
Alopecia
Myelosuppression (bone marrow suppression)
What are the chronic side effects of radiotherapy
Skin: ischaemia, ulceration
Bone: necrosis and fracture
Mouth: Sialitis and ulceration
Bowel: stenosis, fistula, diarrhoea
Bladder: cystitis
Vagina: Stenosis
Lung: fibrosis
Heart: pericardial fibrosis, cardiomyopathy
CNS: myelopathy (spinal cord)
What is the rationale of chemotherapy
- Systemic treatment for advanced cancers: sometimes only sole treatment for advanced cancers like leukaemia
- Majority of solid tumours: chemotherapy for reducing disease volume and palliative symptoms- good in fast growing tumour phase
- Used as adjuvant after primary tumour has been controlled by surgery or radiotherapy
- Form: systemically, intravenously or orally
When is adjuvant therapy given
In absence of macroscopic evidence of metastases to patients at risk of recurring micro-metastases
How are micro-metastases spread
Lymphatic or haematological dissemination
What are the different ways/possibilities for chemotherapy in targeting cancer
- Synergistic drugs: Oxaliplatin (targets DNA) and 5-fluorouracil (stops DNA building blocks)
- Use of drugs combination to kill cancer cells at different cell cycle stages
- Alternating cycles of different drugs from less effective to stronger then repeat (allows tissue time to recover)
Give examples of chemotherapy drugs to target each stage of the cell cycle
- G1: synthesis of DNA components
- Use of anti-metabolites such as Methotrexate, Azathioprine, 6-MP - S phase: DNA synthesis
- Alkylating agents, anti-tumour antibiotics, platinum compounds - G2 Phase: synthesis of components for cell division: use of microtubule inhibitors- stops making components needed to separate
- VINCA ALKALOIDS, Docetaxol, vincristine - Inhibition of RNA synthesis
Doxorubicin
What are the chemotherapy side effects experienced from cytotoxic drugs and explain each one
- Myelosuppression: rapid fall in peripheral blood count with a low point for white cells and platelets at 7 days
- Leucopenia: reduction in white cells leads to immunosuppression
- Thrombocytopenia (reduced platelet count): impairs coagulation leading to bruising and bleeding
- GI and bladder: erosion in mucous membranes
- Falling out of skin and hair
- Fertility: spermatogenesis is inhibited (alkylating agents)- can also cause genetic damage
- Teratogenic action: first trimester affected
What are the side effects experienced from chemotherapy drugs in general
Nausea and vomiting: stimulation of chemoreceptor leads to patients not wanting to continue therapy: Methotrexate, fluorouracil, doxorubicin, cisplatin
Other effects: class of drugs with its own characteristic adverse effect on major organs
Bone Marrow: immunosuppression, bleeding, anaemia, almost all drugs
GI tract: mucositis, ulceration, diarrhoea
Liver: cirrhosis, fibrosis (methotrexate)
How do you minimise side effects?
- Reduce discomfort, morbidity and mortality or to increase tolerable dose threshold
- Close monitoring: important in particular blood counts (patients can be immunocompromised)
- Allowing adequate recovery between treatments
- Forced diuresis: given when nephrotoxic or bladder toxic drugs are given- involves modest over hydration before therapy followed with diuretic.
How do you counteract myelosuppresion and growth factors
Myelosuppresion: blood transfusion, blood platelets, granulocytes
GF: Filgrastism
Timing of doses:
Give examples of antiemetics used
Prochlorperazine
Ondansteron
Lorazepam
Metoclopramide
Dexamethasone
How do you counteract a antifolate overdose
Folinic acid
What is a partial response
More than 50% reduction in tumour
What is a stable disease
No change or <50% reduction and <25% increase
What is progressive disease
Increase in size or tumour by at least 25% of site
